Faculty Research

Ebright, Richard H.

 

 

 

Richard H. Ebright Cayambe r

Board of Governors Professor of Chemistry and Chemical Biology

Research Synopsis: structural biology; single-molecule biophysics; RNA polymerases; antibacterial agents; antituberculosis agents 

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(848) 445-5179

laboratory webpage: https://www.waksman.rutgers.edu/ebright


 

 

Research Summary

Transcription--the synthesis of an RNA copy of genetic information in DNA--is the first step in gene expression and is the step at which most regulation of gene expression occurs. Richard H. Ebright's laboratory seeks to understand structures, mechanisms, and regulation of bacterial transcription complexes and to identify, characterize, and develop small-molecule inhibitors of bacterial transcription for application as antituberculosis agents and broad-spectrum antibacterial agents.

Structures of Transcription Complexes

Transcription initiation in bacteria requires RNA polymerase (RNAP) and the transcription initiation factor sigma. The bacterial transcription initiation complex contains six polypeptides (five in RNAP, one in sigma) and promoter DNA, and has a molecular mass of 0.5 MDa.

Understanding bacterial transcription initiation requires understanding the structures of polypeptides in bacterial transcription initiation complexes and the arrangements of these polypeptides relative to each other and relative to promoter DNA.

The Ebright lab uses x-ray crystallography to determine high-resolution structures of transcription initiation complexes, fluorescence resonance energy transfer (FRET) to define distances between pairs of site specifically incorporated fluorescent probes, photocrosslinking to define polypeptides near site-specifically incorporated photocrosslinking probes, and protein footprinting and residue scanning to define residues involved in contacts. In support of these activities, the lab develops procedures to incorporate fluorescent probes, photocrosslinking probes, and other biophysical and biochemical probes at specific sites within large multisubunit nucleoprotein complexes and develops automated docking algorithms to integrate structural, biophysical, biochemical, and genetic data in order to construct models for structures of complexes.

Structures of Transcription Complexes v2

Crystal structure of the bacterial transcription initiation complex. (A) Summary of protein-nucleic-acid interactions. Black residue numbers and lines, interactions by RNA polymerase (RNAP); green residue numbers and lines; interactions by the transcription initiation factor σ, blue, -10 element of DNA nontemplate strand; light blue, discriminator element of DNA nontemplate strand; pink, rest of DNA nontemplate strand; red, DNA template strand; magenta, ribodinucleotide primer GpA; violet, active-center Mg2+; asterisks, water-mediated interactions; cyan boxes, bases unstacked and inserted into pockets. Residues are numbered as in E coli RNAP and σ70. (B) Overall structure (RNAP β' non conserved domain omitted for clarity). RNAP, gray; σ, yellow. Other colors as in A. (C) Interactions of RNAP and σ with the transcription-bubble nontemplate strand, the transcription bubble template strand, and downstream dsDNA (RNAP β subunit and β' non conserved domain omitted for clarity). Colors as in B.

[See Zhang, Y., Feng, Y., Chatterjee, S., Tuske, S., Ho, M., Arnold, E., and Ebright, R.H. (2012) Structural basis of transcription initiation. Science 338:1076-1080.]

Mechanism of Transcription

Transcription complexes are molecular machines that carry out complex, multistep reactions in transcription initiation and elongation:

  1. RNA polymerase (RNAP) binds to promoter DNA, to yield an RNAP-promoter closed complex.
  2. RNAP unwinds ~14 base pairs of promoter DNA surrounding the transcription start site, rendering accessible the genetic information in the template strand of DNA, and yielding an RNAP-promoter open complex.
  3. RNAP begins synthesis of RNA as an RNAP-promoter initial transcribing complex. During initial transcription, RNAP uses a "scrunching" mechanism, in which RNAP remains stationary on promoter DNA and unwinds and pulls downstream DNA into itself and past its active center in each nucleotide-addition cycle, resulting in generation of a stressed intermediate.
  4. After RNAP synthesizes an RNA product ~10-15 nucleotides in length, RNAP breaks its interactions with promoter DNA, breaks at least some of its interactions with sigma, escapes the promoter, and begins transcription elongation as a transcription elongation complex. Energy stored in the stressed intermediate generated by scrunching during initial transcription is used to drive breakage of interactions with promoter DNA and interactions with sigma during promoter escape.

During transcription elongation, RNAP uses a "stepping" mechanism, in which RNAP translocates relative to DNA in each nucleotide-addition step. Each nucleotide-addition cycle during initial transcription and transcription elongation can be subdivided into four sub-steps: (1) translocation of the RNAP active center relative to DNA (by scrunching in initial transcription; by stepping in transcription elongation); (2) binding of the incoming nucleotide; (3) formation of the phosphodiester bond; and (4) release of pyrophosphate.

Crystal structures have been reported for transcription elongation complexes without incoming nucleotides and for transcription elongation complexes with incoming nucleotides. Based on these crystal structures, it has been proposed that each nucleotide-addition cycle is coupled to an RNAP active-center conformational cycle, involving closing of the RNAP active center upon binding of the incoming nucleotide, followed by opening of the RNAP active center upon formation of the phosphodiester bond. According to this proposal, the closing and opening of the RNAP active center is mediated by the folding and the unfolding of an RNAP active-center structural element, the "trigger loop."

To understand transcription initiation, transcription elongation, and transcriptional regulation, it will be necessary to leverage the available crystallographic structural information, in order to define the structural transitions in RNAP and nucleic acid in each reaction, to define the kinetics of each reaction, and to define mechanisms of regulation of each reaction.

The Ebright lab is using FRET and photocrosslinking methods to define distances and contacts within trapped intermediates in transcription initiation and transcription elongation. In addition, the lab is using single-molecule FRET, single-molecule DNA nanomanipulation, and combined single-molecule FRET and single-molecule DNA nanomanipulation, to carry out single-molecule, millisecond-to-second timescale analysis of structural transitions.

Structures of Transcription Complexes r

Determination of RNAP clamp conformation in solution. (A) Measurement of single-molecule FRET between fluorescent probes incorporated at the tips of the RNAP β’ pincer (clamp) and the RNAP β pincer. Open (red), partly closed (yellow), and closed (green) RNAP clamp conformational states are as observed in crystal structures. (B) Incorporation of fluorescent probes at the tips of the RNAP β’ pincer (clamp) and the RNAP β pincer, by unnatural amino acid mutagenesis to incorporate 4 azidophenylalanine at sites of interest in β’ and β subunits, followed by Staudinger ligation to incorporate fluorescent probes at 4 azidophenylalanines in β’ and β subunits, followed by in vitro reconstitution of RNAP from labelled β’ and β subunits and unlabelled α and ω subunits. (C) Relationship between single-molecule FRET efficiencies, E, and RNAP clamp conformational states. The red boxes denote the open (red), closed (green), and collapsed (blue) clamp states observed in this work for RNAP in solution.

[See Chakraborty, A., Wang, D., Ebright, Y., Korlann, Y., Kortkhonjia, E., Kim, T., Chowdhury, S., Wigneshweraraj, S., Irschik, H., Jansen, R., Nixon, B.T., Knight, J., Weiss, S., and Ebright, R. (2012) Opening and closing of the bacterial RNA polymerase clamp. Science 337, 591-595.]

Regulation of Transcription

Regulation of TranscriptionCrystal structure of a transcriptional activator (catabolite activator protein, CAP; cyan) in complex with its target in the transcriptional machinery (RNA polymerase α-subunit C-terminal domain,αCTD; green) and DNA (red). There are no large-scale conformational changes in the activator and target, and the interface between the activator and target is small (residues highlighted in navy and yellow)—consistent with the proposal that transcriptional activation involves a simple "recruitment" mechanism.

[See Benoff, B., Yang, H., Lawson, C.L., Parkinson, G., Liu, J., Blatter, E., Ebright, Y.W., Berman, H.M., and Ebright, R.H. 2002. Science 297:1562-1566.]

The activities of bacterial transcription initiation complexes are regulated in response to environmental, cell-type, and developmental signals. In most cases, regulation is mediated by factors that bind to specific DNA sites in or near a promoter and inhibit (repressors) or stimulate (activators) one or more of the steps on the transcription initiation pathway. To provide the first complete structural and mechanistic descriptions of activation, the Ebright lab studies two of the simplest examples of activation in bacteria: (1) activation of the lac //promoter by catabolite activator protein (CAP) and (2) activation of the gal promoter by CAP. These model systems each involve only a single activator molecule and a single activator DNA site and, as such, are more tractable than typical examples of activation in bacteria and substantially more tractable than typical examples of activation in eukaryotes (which can involve tens of activator molecules and activator DNA sites).

The lab has established that activation at lac involves an interaction between CAP and the RNA polymerase (RNAP) alpha-subunit C-terminal domain that facilitates closed-complex formation. Activation at gal involves this same interaction and also interactions between CAP and the RNAP alpha-subunit N-terminal domain, and between CAP and sigma, that facilitate isomerization of closed complex to open complex.

Together with collaborators, the lab is using electron microscopy, x-ray crystallography, and NMR to determine the structures of the interfaces between CAP and its targets on RNAP. In addition, the lab is using FRET, photocrosslinking, and single-molecule FRET and single-molecule DNA nanomanipulation methods to define when each CAP-RNAP interaction is made as RNAP enters the promoter and when each interaction is broken as RNAP leaves the promoter.

Inhibitors of Transcription; Antibacterial Drug Discovery

Bacterial RNA polymerase (RNAP) is a proven target for broad-spectrum antibacterial therapy. The suitability of bacterial RNAP as a target for broad-spectrum antibacterial therapy follows from the fact that bacterial RNAP is an essential enzyme (permitting efficacy), the fact that bacterial RNAP-subunit sequences are highly conserved (providing a basis for broad-spectrum activity), and the fact that bacterial RNAP-subunit sequences are not highly conserved in human RNAPI, RNAPII, and RNAPIII (providing a basis for therapeutic selectivity). The rifamycin antibacterial agents--rifampin, rifapentine, rifabutin, and rifamixin--bind to and inhibit bacterial RNAP. The rifamycins bind to a site on bacterial RNAP adjacent to the RNAP active center and prevent extension of RNA chains beyond a length of 2–3 nucleotides. The rifamycins are in current clinical use in treatment of Gram-positive and Gram-negative bacterial infections. The rifamycins are of particular importance in treatment of tuberculosis; the rifamycins are first-line antituberculosis agents and are among the only antituberculosis agents able to clear infection and prevent relapse. The clinical utility of the rifamycin antibacterial agents is threatened by the existence of bacterial strains resistant to rifamycins. Resistance to rifamycins typically involves substitution of residues in or adjacent to the rifamycin-binding site on bacterial RNAP--i.e., substitutions that directly interfere with rifamycin binding.

In view of the public health threat posed by drug-resistant and multidrug-resistant bacterial infections, there is an urgent need for new classes of broad-spectrum antibacterial agents that (1) target bacterial RNAP (and thus have the same biochemical effects as rifamycins), but that (2) target sites within bacterial RNAP that do not overlap the rifamycin-binding site (and thus do not show cross-resistance with rifamycins).

The Ebright lab has identified new drug targets within the structure of bacterial RNAP. Each of these new targets can serve as a potential binding site for compounds that inhibit bacterial RNAP and thereby kill bacteria. Each of these new targets is present in most or all bacterial species, and thus compounds that bind to these new targets are active against a broad spectrum of bacterial species. Each of these new targets is different from targets of current antibiotics, and thus compounds that bind to these new targets are not cross-resistant with current antibiotics. For each of these new targets, the lab has identified at least one lead compound that binds to the target, and the lab has synthesized analogs of the lead compound comprising optimized lead compounds. Several of the lead compounds and optimized lead compounds are extremely promising: they exhibit potent activity against a broad spectrum of bacterial pathogens (including Staphylococcus aureus MSSA, Staphylococcus aureus MRSA, Enterococcus faecalis, Enterococcus faecium, Clostridium difficile, Mycobacterium tuberculosis, Bacillus anthracis, Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei) and exhibit no cross-resistance with current antibiotics.

In support of this work, the lab is identifying new small-molecule inhibitors of bacterial RNAP by analysis of microbial and plant natural products, by high-throughput screening, and by virtual screening. The lab also is using genetic, biochemical, biophysical, and crystallographic approaches to define the mechanism of action of each known, and each newly identified, small-molecule inhibitor of bacterial RNAP, and the lab is using microbiological approaches to define antibacterial efficacies, resistance spectra, and spontaneous resistance frequencies of known and new small-molecule inhibitors of bacterial RNAP.

The lab seeks to address the following objectives: to develop new classes of antituberculosis agents and broad-spectrum antibacterial agents, to develop antibacterial agents effective against pathogens resistant to current antibiotics, to develop antibacterial agents effective against pathogens of high relevance to public health, and to develop antibacterial agents effective against pathogens of high relevance to biodefense.

Small Molecule Inhibitors of Bacterial TranscriptionStructural basis of transcription inhibition by myxopyronin: contacts between RNA polymerase and myxopyronin.

  1. Binding pocket for myxopyronin. Cyan, surface representation of the binding pocket and adjacent hydrophobic pocket. Gray, ribbon representation of RNA polymerase backbone. Green, myxopyronin carbon atoms; red, myxopyronin oxygen atoms. RNA polymerase residues are numbered both as in T thermophilus RNA polymerase and as in E. coli RNA polymerase (in parentheses).
  2. Contacts between RNA polymerase and myxopyronin (stereoview). Gray, RNA polymerase backbone (ribbon representation) and RNA polymerase sidechain carbon atoms (stick representation); green, myxopyronin carbon atoms; red, oxygen atoms; blue, nitrogen atoms. "W," ordered bound water molecule. Dashed lines, H-bonds.
  3. Schematic summary of contacts between RNA polymerase and myxopyronin. "W", ordered bound water molecule. Red dashed lines, H-bonds. Blue arcs, van der Waals interactions.

[See Mukhopadhyay, J., Das, ., Ismail, S., Koppstein, D., Jang, M., Hudson, B., Sarafianos, S., Tuske, S., Patel, J., Jansen, R., Irschik, H., Arnold, E., and Ebright, R. (2008) The RNA polymerase "switch region" is a target of inhibitors Cell 135, 295-307.]

Publications

Ebright, R., Cossart, P., Gicquel-Sanzey, B., and Beckwith, J. (1984) Mutations that alter the DNA sequence specificity of the catabolite gene activator protein of E. coli. Nature 311, 232-235.

Ebright, R., Cossart, P., Gicquel-Sanzey, B., and Beckwith, J. (1984) Molecular basis of DNA sequence recognition by the catabolite gene activator protein: detailed inferences from three mutations that alter DNA sequence specificity. Proc. Natl. Acad. Sci. USA 81, 7274-7278.

Ebright, R., Le Grice, S., Miller, J., and Krakow, J. (1985) Analogs of cyclic AMP that elicit the biochemically defined conformational change in catabolite gene activator protein (CAP) but do not stimulate binding to DNA. J. Mol. Biol. 182, 91-107.

Ebright, R. and Beckwith, J. (1985) The catabolite gene activator protein (CAP) is not required for indole-3-acetic acid to activate transcription of the araBAD operon of Escherichia coli K-12. Mol. Gen. Genet. 201, 51-55.

Ebright, R. (1985) Use of "loss-of-contact" substitutions to identify residues involved in an amino acid-base pair contact: effect of substitution of Gln18 of lac repressor by Gly, Ser, and Leu. J. Biomol. Struct. Dyn. 3, 281-297.

Ebright, R. (1986) Evidence for a contact between glutamine-18 of lac repressor and base pair 7 of lac operator. Proc. Natl. Acad. Sci. USA 83, 303-307.

Ebright, R., Wong, J., and Chen L.B. (1986) Binding of 2-hydroxybenzo(a)pyrene to estrogen receptors in rat cytosol. Cancer Res. 46: 2349-2351.

Ebright, R., Kolb, A., Buc, H., Kunkel, T., Krakow, J., and Beckwith, J. (1987) Role of glutamic acid 181 in DNA-sequence recognition by the catabolite gene activator protein (CAP) of Escherichia coli. Proc. Natl. Acad. Sci. USA 84, 6083-6087.

Ebright, R., Ebright, Y., and Gunasekera, A. (1989) Consensus DNA site for the Escherichia coli catabolite gene activator protein (CAP): CAP exhibits a 450-fold higher affinity for the consensus DNA site than for the E. coli lac DNA site. Nucleic Acids Res. 17, 10295-10305.

Ebright, R., Ebright, Y., Pendergrast, P.S., and Gunasekera, A. (1990) Conversion of a helix-turn-helix motif sequence-specific DNA binding protein into a site-specific DNA cleavage agent. Proc. Natl. Acad. Sci. USA 87, 2882-2886.

Ebright, R., Gunasekera, A., Zhang, X., Kunkel, T., and Krakow, J. (1990) Lysine 188 of the catabolite gene activator protein (CAP) plays no role in specificity at base pair 7 of the DNA half site. Nucleic Acids Res. 18, 1457-1464

Zhang, X. and Ebright, R. (1990) Identification of a contact between arginine-180 of the catabolite gene activator protein (CAP) and base pair 5 of the DNA site in the CAP-DNA complex. Proc. Natl. Acad. Sci. USA 87, 4717-4721.

Zhang, X. and Ebright, R. (1990) Substitution of two base pairs (one base pair per DNA half site) within the Escherichia coli lac promoter DNA site for catabolite gene activator protein places the lac promoter in the FNR regulon. J. Biol. Chem. 265, 12400-12403.

Gunasekera, A., Ebright, Y. and Ebright, R. (1990) DNA-sequence recognition by CAP: Role of the adenine N6 atom of base pair 6 of the DNA site. Nucleic Acids Res. 18, 6853-6856.

Zhang, X., Gunasekera, A., Ebright, Y., and Ebright, R. (1991) Derivatives of CAP having no solvent-accessible cysteine residues, or having a unique solvent-accessible cysteine residue at amino acid 2 of the helix-turn-helix motif of CAP. J. Biomol. Struct. Dyn. 9, 463-473.

Shin, J., Ebright, R., and Dervan, P. (1991) Orientation of the Lac repressor DNA binding domain in complex with the left lac operator half site characterized by affinity cleaving. Nucleic Acids Res. 19, 5233-5236.

Zhou, Y., Zhang, X., and Ebright, R. (1991) Random mutagenesis of gene-sized DNA molecules by use of PCR with Taq DNA polymerase. Nucleic Acids Res. 19, 6052.

Ebright, R. (1991) Identification of amino acid-base pair contacts by genetic methods. Meths. Enzymol. 208, 620‑640.

Zhang, X., Zhou, Y., Ebright, Y., and Ebright, R. (1992) CAP is not an "acidic activating region" transcription activator protein: negatively charged amino acids of CAP that are solvent-accessible in the CAP-DNA complex play no role in transcription activation at the lac promoter. J. Biol. Chem. 267, 8136‑8139.

Gunasekera, A., Ebright, Y. and Ebright, R. (1992) DNA-sequence determinants for binding of the Escherichia coli catabolite gene activator protein (CAP). J. Biol. Chem. 267, 14713-14720.

Dong, Q. and Ebright, R. (1992) DNA binding specificity and sequence of Xanthomonas campestris catabolite gene activator protein-like protein. J. Bacteriol. 174, 5757-5461.

Ebright, R., Dong, Q., and Messing, J. (1992) Corrected nucleotide sequence of M13mp18 gene III. Gene 114, 81-3.

Blatter, E., Ebright, Y., and Ebright, R. (1992) Identification of an amino acid-base contact in the GCN4-DNA complex by bromouracil-mediated photocrosslinking. Nature 359, 650-652.

Pendergrast, P.S., Chen, Y., Ebright, Y., and Ebright, R. (1992) Determination of the orientation of a DNA binding motif in a protein-DNA complex by photocrosslinking. Proc. Natl. Acad. Sci. USA 89, 10287-10291.

Ebright, Y., Chen, Y., Pendergrast, P.S., and Ebright, R. (1992) Incorporation of an EDTA-metal complex at a rationally selected site within a protein: application to EDTA-iron affinity cleaving with catabolite gene activator protein (CAP) and Cro. Biochem. 31, 10664-10670.

Chen, Y. and Ebright, R. (1993) Phenyl-azide-mediated photocrosslinking analysis of Cro-DNA interaction. J. Mol. Biol. 230, 453-460.

Ebright, Y., Chen, Y., Ludescher, R., and Ebright, R. (1993) Iodoacetyl-p-phenylenediamine-EDTA: Reagent for high-efficiency incorporation of an EDTA-metal complex at a rationally selected site within a protein.   Bioconj. Chem. 4, 219-225.

Ebright, R. (1993) Transcription activation at class I CAP-dependent promoters. Mol. Microbiol. 8, 797‑802.

Zhou, Y., Zhang, X., and Ebright, R. (1993) Identification of the activating region of CAP: isolation and characterization of mutants of CAP specifically defective in transcription activation. Proc. Natl. Acad. Sci. USA 90, 6081-6085.

Zhou, Y., Busby, S., and Ebright, R. (1993) Identification of the functional subunit of a dimeric transcription activator protein by use of "oriented heterodimers." Cell 73, 375-379.

Heyduk, T., Lee, J., Ebright, Y., Blatter, E., Zhou, Y., and Ebright, R. (1993) CAP interacts with RNA polymerase in solution in the absence of promoter DNA. Nature 364, 548-549.

Shang, Z., Ebright, Y., Iler, N., Pendergrast, P.S., Echelard, Y., McMahon, A., Ebright, R., and Abate, C. (1994) DNA affinity cleaving analysis of homeodomain-DNA interaction: Identification of homeodomain consensus DNA sites in genomic DNA. Proc. Natl. Acad. Sci. USA 91, 118-122.

Dong, Q., Blatter, E., Ebright, Y., Bister, K., and Ebright, R. (1994) Identification of amino acid‑base contacts in the Myc-DNA complex by site-specific bromouracil-mediated photocrosslinking. EMBO J. 13, 200-204.

Chen, Y., Ebright, Y., and Ebright, R. (1994) Identification of the target of a transcription activator protein by protein-protein photocrosslinking.   Science 265, 90-92.

Pendergrast, P.S., Ebright, Y., and Ebright, R. (1994) High-specificity DNA cleavage agent: design and application to kilobase and megabase DNA substrates. Science 265, 959-961.

Blatter, E., Ross, W., Tang, H., Gourse, R., and Ebright, R. (1994) Domain organization of RNA polymerase a subunit: C-terminal 85 amino acids constitute a domain capable of dimerization and DNA binding. Cell 78, 889-896.

Zhou, Y., Pendergrast, P.S., Bell, A., Williams, R., Busby, S., and Ebright, R. (1994) The functional subunit of a dimeric transcription activator protein depends on promoter architecture. EMBO J. 13, 4549‑4557.

Niu, W., Zhou, Y., Dong, Q., Ebright, Y., and Ebright, R. (1994) Characterization of the activating region of Escherichia coli catabolite gene activator protein (CAP): I. Saturation and alanine‑scanning mutagenesis. J. Mol. Biol. 243, 595-602.

Zhou, Y., Merkel, T., and Ebright, R. (1994) Characterization of the activating region of Escherichia coli catabolite gene activator protein (CAP): II. Role at Class I and Class II CAP-dependent promoters. J. Mol. Biol. 243, 603-610.

Busby, S. and Ebright, R. (1994) Promoter structure, promoter recognition, and transcription activation in prokaryotes. Cell 79, 743-746.

Tang, H., Severinov, K., Goldfarb, A., Fenyo, D., Chait, B, and Ebright, R. (1994) Location, structure, and function of the target of a transcriptional activator protein. Genes & Development 8, 3058-3067.

Merkel, T., Dahl, J., Ebright, R., and Kadner, R. (1995) Transcription activation at the Escherichia coli uhpT promoter by the catabolite gene activator protein. J. Bact. 177, 1712-1718.

Ebright, R. and Busby, S. (1995) Escherichia coli RNA polymerase a subunit: structure and function. Curr. Opin. Genet. Development 5, 197-203.

Tang, H., Severinov, K., Goldfarb, A, and Ebright, R. (1995) Rapid RNA polymerase genetics: one‑day, no-column preparation of reconstituted recombinant Escherichia coli RNA polymerase. Proc. Natl. Acad. Sci. USA 92, 4902‑4906.

Gaal, T., Ross, W., Blatter, E., Tang, H., Jia, X., Krishnan, V., Assa-Munt, N., Ebright, R., and Gourse, R. (1996) DNA binding determinants of the a subunit of RNA polymerase: a novel DNA binding domain architecture. Genes & Development 10, 16-26.

Tang, H., Sun, X., Reinberg, D. and Ebright, R. (1996) Protein-protein interactions in eukaryotic transcription initiation: structure of the pre-initiation complex. Proc. Natl. Acad. Sci. USA 93, 1119‑1124.

Dumoulin, P., Ebright, R., Knegtel, R., Kaptein, R., Granger-Schnarr, M. and Schnarr, M. (1996) Structure of the LexA-DNA complex probed by affinity cleavage and affinity photocrosslinking. Biochem. 35, 4279‑4286

Ebright, Y., Chen, Y., Kim, Y. and Ebright, R. (1996) S-[2-(4-azidosalicylamido)ethanethio]-2-thiopyridine: radioiodinatable, cleavable photoactivatible crosslinking agent. Bioconj. Chem. 7, 380‑384.

Sheehan, B., Klarsfeld, A., Ebright, R. and Cossart, P. (1996) A single substitution in the putative helix-turn-helix motif of the pleiotropic activator PrfA attenuates Listeria monocytogenes virulence. Mol. Microbiol. 20, 785-797.

Pellegrini, M. and Ebright, R. (1996) Artificial DNA binding peptides: branched-chain basic regions. J. Amer. Chem. Soc. 118, 5831-5835.

Parkinson, G., Wilson, C., Gunasekera, A., Ebright, Y., Ebright, R. and Berman, H. (1996) Structure of the CAP-DNA complex at 2.5 Å resolution: a complete picture of the protein-DNA interface. J. Mol. Biol. 260, 395-408.

Parkinson, G., Gunasekera, A., Vojtechovsky, J., Zhang, X., Kunkel, T., Berman, H. and Ebright, R. (1996) Aromatic hydrogen bond in sequence-specific protein-DNA interaction. Nature Structl. Biol. 3, 837-841.

Heyduk, T., Heyduk, E., Severinov, K., Tang, H. and Ebright, R. (1996) Determinants of RNA polymerase a subunit for interaction with b and b' subunits: hydroxyl‑radical protein footprinting. Proc. Natl. Acad. Sci. USA 93, 10162‑10166.

Lagrange, T., Kim, T.-K., Orphanides, G. Ebright, Y., Ebright, R., and Reinberg, D. (1996) High‑resolution mapping of nucleoprotein complexes by site-specific protein-DNA photocrosslinking: organization of the human TBP‑TFIIA‑TFIIB-DNA quaternary complex. Proc. Natl. Acad. Sci. USA 93, 10620-10625.

Ebright, R., Ebright, Y., and Pendergrast, P.S. (1996) CAP-phenanthroline conjugate for DNA cleavage. US Patent US5556949.

Tang, H., Kim, Y., Severinov, K., Goldfarb, A., and Ebright, R. (1996) Escherichia coli RNA polymerase holoenzyme: rapid reconstitution from recombinant a, b, b', and s subunits. Meths. Enzymol. 273, 130‑134.

Heyduk, T., Ma, Y., Tang, H., and Ebright, R. (1996) Fluorescence anisotropy: rapid, quantitative assay for protein-DNA and protein-protein interaction. Meths. Enzymol. 274, 492-503.

Niu, W., Kim, Y., Tau, G., Heyduk, and Ebright, R. (1996) Transcription activation at Class II CAP‑dependent promoters: two interactions between CAP and RNA polymerase. Cell 87, 1123‑1134.

Busby, S. and Ebright, R. (1997) Transcription activation at Class II CAP-dependent promoters. Mol. Microbiol. 23, 853-859.

Miller, A., Wood, D., Ebright, R., and Rothman-Denes, L. (1997) RNA polymerase b': a target for DNA‑binding-independent activation. Science 275, 1655-1657.

Kim, T.-K., Lagrange, T., Wang, Y.-W., Griffith, J., Reinberg, D., and Ebright, R. (1997) Trajectory of DNA in the RNA polymerase II transcription preinitiation complex. Proc. Natl. Acad. Sci. USA 94, 12268-12273.

Lagrange, T., Kapanidis, A., Tang, H., Reinberg, D. and Ebright, R. (1998) New core promoter element in RNA-polymerase-II-dependent transcription: sequence-specific DNA binding by transcription factor IIB. Genes & Development 12, 34-44.

Savery, N., Lloyd, G., Kainz, M., Gaal, T., Ross, W., Ebright, R., Gourse, R. and Busby, S. (1998) Transcription activation at Class II CRP-dependent promoters: identification of determinants in the C‑terminal domain of the RNA polymerase a subunit EMBO J. 17, 3439-3447.

Sullivan, S., Horn, P., Olson, V., Koop, A., Niu, W., Ebright, R., and Triezenberg, S. (1998) Mutational analysis of the transcriptional activation region of the VP16 protein of herpes simplex virus. Nucl. Acids Res. 26, 4487-4496.

Harrison-McMonagle, P., Denissova, N., Martinez-Hackert, E., Ebright, R., and Stock, A. (1999) Orientation of OmpR monomers within an OmpR-DNA complex determined by DNA affinity cleaving. J. Mol. Biol. 285, 555-566.

Estrem, S., Ross, W., Gaal., Chen, Z.W.S., Niu, W., Ebright, R., and Gourse, R. (1999) Bacterial promoter architecture: subsite structure of UP elements and interactions with the carboxyl-terminal domain of RNA polymerase a subunit. Genes & Development 13, 2134-2147.

Busby, S. and Ebright, R. (1999) Transcription activation by catabolite activator protein (CAP). J. Mol. Biol. 293, 199-213.

Tan, Q., Linask, K.L., Ebright, R. and Woychik, N. (2000) Activation mutants in yeast RNA polymerase subunit RPB3 provide evidence for a structurally conserved surface required for activation in eukaryotes and bacteria. Genes & Development 14, 339-348.

Boyer, L., Shao, X., Ebright, R., and Peterson, C. (2000) Roles of the histone H2A/H2B dimers and (H3/H4)2 tetramer in nucleosome remodeling by SWI/SNF complex. J. Biol. Chem. 275, 11545‑11552.

Meibom, K., Kallipolitis, B., Ebright, R., and Valentin-Hansen, P. (2000) Identification of the subunit of CRP that functionally interacts with CytR in CRP-CytR-mediated transcriptional repression. J. Biol. Chem. 275, 12123-12128.

Kim, T.-K., Ebright, R., and Reinberg, D. (2000) Mechanism of ATP-dependent promoter melting by transcription factor IIH. Science 288, 1418-1421.

Naryshkin, N., Revyakin, A., Kim, Y., Mekler, V., and Ebright, R. (2000) Structural organization of the RNA polymerase-promoter open complex. Cell 101, 601-611.

Ebright, R. (2000) RNA polymerase: structural similarities between bacterial RNA polymerase and eukaryotic RNA polymerase II. J. Mol. Biol. 304, 687-698.

Naryshkin, N., Kim, Y., Dong, Q., and Ebright, R. (2001) Site-specific protein-DNA photocrosslinking: analysis of bacterial transcription initiation complexes. Meths. Mol. Biol. 148, 336-361.

Minakhin, L., Bhagat, S. Brunning, A., Campbell, E., Darst, S., Ebright, R. and Severinov, K. (2001) Bacterial RNA polymerase subunit w and eukaryotic RNA polymerase subunit RPB6 are sequence, structural, and functional homologs and promote RNA polymerase assembly Proc. Natl. Acad. Sci. USA 98, 892-897.

Mukhopadhyay, J., Kapanidis, A., Mekler, V., Kortkhonjia, E., Ebright, Y., and Ebright, R. (2001) Translocation of s70 with RNA polymerase during transcription: fluorescence resonance energy transfer assay for movement relative to DNA. Cell 106, 453-463.

Kapanidis, A., Ebright, Y., Ludescher, R., Chan, S., and Ebright, R. (2001) Mean DNA bend angle and distribution of DNA bend angles in the CAP-DNA complex in solution. J. Mol. Biol. 312, 453‑468.

Chen, S., Vojtechovsky, J., Parkinson, G., Ebright, R., and Berman, H. (2001) Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex: I. DNA binding specificity based on energetics of DNA kinking. J. Mol. Biol. 314, 63-74.

Chen, S., Gunasekera, A., Zhang, X., Kunkel, T., Ebright, R., and Berman, H. (2001) Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex: II. Alteration of DNA binding specificity through alteration of DNA kinking. J. Mol. Biol. 314, 75-82.

Kapanidis, A., Ebright, Y., and Ebright, R. (2001) Site-specific incorporation of fluorescent probes into protein: hexahistidine-tag-mediated fluorescent labeling using (Ni++:nitrilotriacetic acid)n-fluorochrome conjugates.   J. Amer. Chem. Soc. 123, 12123-12125.

Mekler, V., Kortkhonjia, E., Mukhopadhyay, J., Knight, J., Revyakin, A., Kapanidis, A., Niu, W., Ebright, Y., Levy, R., and Ebright, R. (2002) Structural organization of bacterial RNA polymerase holoenzyme and the RNA polymerase-promoter open complex. Cell 108, 599-614.

Savery, N., Lloyd, G., Busby, S., Thomas, M., Ebright, R., and Gourse, R. (2002) Determinants of the C‑terminal domain of the Escherichia coli RNA polymerase a subunit important for transcription at Class I cyclic AMP receptor protein-dependent promoters. J. Bacteriol. 184, 2273-2280.

Benoff, B., Yang, H., Lawson, C., Parkinson, G., Liu, J., Blatter, E., Ebright, Y., Berman, H., and Ebright, R. (2002) Structural basis of transcription activation: the CAP-aCTD-DNA complex. Science 297, 1562‑1566.

Lloyd, G., Niu, W., Trebbutt, J., Ebright, R., and Busby, S. (2002) Requirement for two copies of RNA polymerase a subunit C-terminal domain for synergistic transcription activation at complex bacterial promoters.   Genes & Development 16, 2557-2565.

Chen, H., Tang, H., and Ebright, R.H. (2003) Functional interaction between RNA polymerase a subunit C-terminal domain and s70 in UP-element- and activator-dependent transcription. Mol. Cell 11, 1621‑1633.

Bayro, M., Mukhopadhyay, J., Swapna, G.V.T., Huang, J., Ma, L.-C., Sineva, E., Dawson, P., Montelione, G., and Ebright, R. (2003) Structure of antibacterial peptide microcin J25: a 21-residue lariat protoknot. J. Amer. Chem. Soc. 125, 12382‑12383.

Revyakin, A., Allemand, J.-F., Croquette, V., Ebright, R., and Strick, T. (2003) Single-molecule DNA nanomanipulation: detection of promoter unwinding events by RNA polymerase. Meths. Enzymol. 370, 577-598.

Mukhopadhyay, J., Mekler, V., Kortkhonjia, E., Kapanidis, A., Ebright, Y., and Ebright, R. (2003) Fluorescence resonance energy transfer (FRET) in analysis of transcription-complex structure and function.   Meths. Enzymol. 371, 144-159.

Seul, M. and Ebright, R. (2003) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. Australian Patent AU756945.

Renfrow, M., Naryshkin, N., Lewis, M., Chen, H.-T., Ebright, R., and Scott, R. (2004) Transcription factor B contacts promoter DNA near the transcription start site of the archaeal transcription initiation complex. J. Biol. Chem. 279, 2825‑2831.

Lawson, C., Swigon, D., Murakami, K., Darst, S., Berman, H., and Ebright, R., (2004) Catabolite activator protein (CAP): DNA binding and transcription activation. Curr. Opin. Structl. Biol. 14, 10-20.

Revyakin, A., Ebright, R., and Strick, T. (2004) Promoter unwinding and promoter clearance by RNA polymerase: Detection by single-molecule DNA nanomanipulation. Proc. Natl. Acad. Sci. USA 101, 4776‑4780.

Nickels, B., Mukhopadhyay, J.,   Garrity, S., Ebright, R., and Hochschild, A. (2004) s70 mediates a promoter-proximal pause at the lac promoter.   Nature Structl. Mol. Biol. 11, 544-550.

Mukhopadhyay, J., Sineva, E., Knight, J., Levy, R., and Ebright, R. (2004) Antibacterial peptide microcin J25 (MccJ25) inhibits transcription by binding within and obstructing the RNA polymerase secondary channel. Mol. Cell. 14, 739-751.

Revyakin, A., Ebright, R.H., and Strick, T. (2005) Single-molecule DNA nanomanipulation: improved resolution through use of shorter DNA fragments. Nature Meths. 2, 127-138.

Knight, J., Mekler, V., Mukhopadhyay, J., Ebright, R., and Levy, R. (2005) Distance-restrained docking of rifampicin and rifamycin SV to RNA polymerase using systematic FRET measurements: developing benchmarks of model quality and reliability. Biophys. J. 88, 925-938.

Lee, N.K., Kapanidis, A., Wang, Y., Michalet, X., Mukhopadhyay, J., Ebright, R.H., and Weiss, S. (2005) Accurate FRET measurements within diffusing single biomolecules using alternating-laser excitation. Biophys. J. 88, 2939‑2953.

Nickels, B. Garrity, S., Mekler, V., Minakhin, L., Severinov, K., Ebright, R.H., and Hochschild, A. (2005) Altering the interaction between s70 and the b-flap of Escherichia coli RNA polymerase provides evidence for a barrier to the extension of the nascent RNA during early elongation. Proc. Natl. Acad. Sci USA 102, 4488‑4493.

Ebright, R. and Ebright, Y. (2005) Bis-transition-metal-chelate probes. US Patent US6919333.

Tuske, S., Sarafianos, S., Wang, X., Hudson, B., Sineva, E., Mukhopadhyay, J., Birktoft, J, Leroy, O., Ismail, S., Clark, A., Dharia, C., Napoli, A., Laptenko, O., Lee, J., Borukhov, S., Ebright, R., and Arnold, E. (2005) Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation. Cell 122, 541-552.

Vrentas, C., Gaal, T., Ross, W., Ebright, R., and Gourse, R. (2005) Response of RNA polymerase to ppGpp: requirement for the w subunit and relief of this requirement by DksA.   Genes Dev. 19, 2378-2387.

Kapanidis, A., Margeat, E., Laurence, T., Doose, S., Ho, S.O., Mukhopadhyay, J., Kortkhonjia, E., Mekler, V., Ebright, R., and Weiss, S. (2005) Retention of transcription initiation factor s70 in transcription elongation: single‑molecule analysis. Mol. Cell 20, 347-356.

Margeat, E., Kapanidis, A., Tinnefield, P., Wang, Y., Mukhopadhyay, J., Ebright, R., and Weiss, S. (2006) Direct observation of abortive initiation and promoter escape within immobilized single transcription complexes. Biophys. J. 20, 347-356.

Napoli, A., Lawson, C., Ebright, R., and Berman, H. (2006)   Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex: recognition of pyrimidine-purine and purine-purine steps. J. Mol Biol. 357, 173‑183.

Tadigotla, V., O'Maoileidigh, D., Sengupta, A., Epshtein, V., Ebright, R., Nudler, E., and Ruckenstein, A. (2006) Thermodynamic and kinetic modeling of transcriptional pausing. Proc. Natl. Acad. Sci. USA 103, 4439-4444.

Seul, M. and Ebright, R. (2006) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. US Patent US7083914.

Popovych, N., Sun, S., Ebright, R., and Kalodimos, C. (2006) Dynamically driven protein allostery. Nature Structl. Mol. Biol. 13, 831-838.

Revyakin, A., Liu, C., Ebright, R.H. and Strick, T. (2006) Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching. Science 314, 1139-1143.

Kapanidis, A., Margeat, E., Ho, S.O., Kortkhonjia, E., Weiss, S. and Ebright, R. (2006) Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism. Science 314, 1144‑1147.

Ebright, R. and Ebright, Y. (2006) Reagents and procedures for high-specificity labelling. US Patent US7141655.

Cellai, S., Vannini, N., Naryshkin, N., Kortkhonjia, E., Ebright, R., and Rivetti, C. (2007) Upstream promoter sequences and aCTD mediate stable DNA wrapping within the RNA polymerase open promoter complex. EMBO Reports 8, 271-278.

Ebright, R. and Ebright, Y. (2007) Ultra-high-specificity fluorescent labelling. US Patent US7282373.

Ebright, R. and Ebright, Y. (2008) Bis-transition-metal-chelate probes. US Patent US7371745.

Ebright, R. and Ebright, Y. (2008) Reagents and procedures for multi-label high-specificity labelling. US Patent US7381572.

Seul, M. and Ebright, R. (2007) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. European Patent EP1003904.

Severinov, K., Ebright, R, Pavlova, O., and Sineva, E. (2008) Mutational derivatives of peptide antibiotic microcin J25. US Patent US7442762.

Pavlova, O., Mukhopadhyay, J., Sineva, E., Ebright, R., and Severinov, K. (2008) Systematic structure-activity analysis of microcin J25 (MccJ25).   J. Biol. Chem. 283, 25589-25595.

Feklistov, A., Mekler, V., Jiang, Q., Westblade, L., Irschik, H., Jansen, R., Mustaev, A., Darst, S., and Ebright, R. (2008)   Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center. Proc. Natl. Acad. Sci. USA 105, 14820-14825.

Mukhopadhyay, J., Das, K., Ismail, S., Koppstein, D., Jang, M., Hudson, B., Sarafianos, S., Tuske, S., Patel, J., Jansen, R., Irschik, H., Arnold, E., and Ebright, R. (2008) The RNA polymerase "switch region" is a target of inhibitors Cell 135, 295-307.

Kim, Y., Ebright, Y., Goodman, A., Reinberg, D., and Ebright, R. (2008) Non-radioactive, ultrasensitive site‑specific protein-protein photocrosslinking: interactions of a-helix 2 of TATA‑binding protein with general transcription factor TFIIA and with transcriptional repressor NC2. Nucl. Acids Res. 36, 6143‑6154.

Naryshkin, N., Druzhinin S., Revyakin, A., Kim, Y., Mekler, V., and Ebright, R. (2009) Static and kinetic site‑specific protein-DNA photocrosslinking: analysis of bacterial transcription initiation complexes. Meths. Mol. Biol. 543, 403-437.

Popovych, N., Tzeng, S.-R., Tonelli, M., Ebright­, R., and Kalodimos, C. (2009) Structural basis of cAMP-mediated allosteric control of the catabolite activator protein, Proc. Natl. Acad. Sci. USA 106, 6927-6932.

Goldman, S., Ebright, R., and Nickels, B. (2009) Direct detection of abortive RNA transcripts in vivo. Science 324, 927-928.

Hudson, B., Quispe, J., Lara, S., Kim, Y., Berman, H., Arnold, E., Ebright, R., and Lawson, C. (2009) Three‑dimensional structure of an intact activator-dependent transcription initiation complex. Proc. Natl. Acad. Sci. USA 106, 19830-19835.

Ho, M., Hudson, B., Das, K., Arnold, E., and Ebright, R. (2009) Structures of RNA polymerase-antibiotic complexes. Curr. Opin. Structl. Biol. 19, 715-723.

Seul, M. and Ebright, R. (2009) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. Japanese Patent JP4302780.

Chakraborty, A., Wang, D., Ebright, Y., and Ebright, R. (2010) Azide-specific labelling of biomolecules by Staudinger-Bertozzi ligation: phosphine derivatives of fluorescent probes suitable for single‑molecule fluorescence spectroscopy. Meths. Enzymol. 472, 19-30.

Grohmann, D., Nagy, J., Chakraborty, A., Klose, D., Fielden, D., Ebright, R., Michaelis, J., and Werner, F. (2011) The initiation factor TFE and the elongation factor Spt4/5 compete for binding to the RNAP clamp during transcription initiation and elongation.   Mol. Cell 43, 263-274.

Xiao, Y., Wei, X., Ebright, R., and Wall, D. (2011) Antibiotic production by myxobacteria plays a role in predation. J. Bacteriol. 193, 4626-4633.

Kuznedelov, K., Semenova, E., Knappe, T., Mukahmedjarov, D., Srivastava, A., Chatterjee, S., Ebright, R., Marahiel, M., and Severinov, K. (2011) The antibacterial threaded-lasso peptide capistruin inhibits bacterial RNA polymerase.   J. Mol. Biol. 412, 842-848.

Srivastava, A., Talaue, M., Liu, S., Degen, D., Ebright, R.Y., Sineva, E., Chakraborty, A., Druzhinin, S., Chatterjee, S., Mukhopadhyay, J., Ebright, Y., Zozula, A., Shen, J., Sengupta, S., Niedfeldt, R., Xin, C., Kaneko, T., Irschik, H., Jansen, R., Donadio, S., Connell, N., and Ebright, R. (2011) New target for inhibition of bacterial RNA polymerase: "switch region." Curr. Opin. Microbiol. 14, 532-543.

Ebright, R. (2012) Switch region: target and method for inhibition of bacterial RNA polymerase. US Patent US8114583.

Ebright, R. (2012) Target and method for inhibition of bacterial RNA polymerase. US Patent US8198021.

Ebright, R. (2012) RNA exit channel: target and method for inhibition of bacterial RNA polymerase. US Patent US8206898.

Chakraborty, A., Wang, D., Ebright, Y., Korlann, Y., Kortkhonjia, E., Kim, T., Chowdhury, S., Wigneshweraraj, S., Irschik, H., Jansen, R., Nixon, B.T., Knight, J., Weiss, S., and Ebright, R. (2012) Opening and closing of the bacterial RNA polymerase clamp. Science 337, 591-595.

Srivastava, A., Degen, D., Ebright, Y., and Ebright, R. (2012) Frequency, spectrum, and nonzero fitness costs of resistance to myxopyronin in Staphylococcus aureus. Antimicrob. Agents Chemother. 56, 6250‑6255.

Zhang, Y., Feng, Y., Chatterjee, S., Tuske, S., Ho, M., Arnold, E., and Ebright, R. (2012) Structural basis of transcription initiation. Science 338, 1076-1080.

Seul, M. and Ebright, R. (2013) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. Canadian Patent CA2291853.

Ebright, R., Mukhopadhyay, J., Severinov, K., and Semenova, E. (2013) Non-MccJ25-related lariat-peptide inhibitors of bacterial RNA polymerase. US Patent US8354246.

Ebright, R. and Wang, D. (2013) Bipartite inhibitors of bacterial RNA polymerase.  US Patent 8372839.

Robb, N., Cordes, T., Hwang, L., Gryte, K., Duchi, D., Craggs, T., Santoso, Y., Weiss, S., Ebright, R., and Kapanidis, A. (2013) The transcription bubble of the RNA polymerase-promoter open complex exhibits conformational heterogeneity and millisecond-scale dynamics: implications for transcription start-site selection. J. Mol. Biol. 425, 875–885.

Ebright, R. and Severinov, K., (2013) Nucleic acid sequences for biosynthesis of non-MccJ25-related lariat peptides.  US Patent 8461314.

Ebright, R. (2013) Target and method for inhibition of bacterial RNA polymerase. US Patent 8575306.

Vorobiev, S., Kramer, Y., Vahedian-Movahed, H., Seetharaman, J., Sua, M., Huang., J., Xiao, R., Kornhaber, G., Montelione, G., Tong, L., Ebright, R., and Nickels, B. (2014) Structure of the DNA‑binding and RNA polymerase‑binding region of transcription antitermination factor Q. Structure 22, 488‑495.

Ebright, R. (2014) RNA exit channel: target and method for inhibition of bacterial RNA polymerase. US Patent 8697354.

Zhang, Y., Degen, D., Ho, M., Sineva, E., Ebright, K., Ebright, Y., Mekler, V., Vahedian-Movahed, H., Feng, Y., Yin, R., Tuske, S., Irschik, H., Jansen, R., Maffioli, S., Donadio, S., Arnold, E., and Ebright, R. (2014) GE23077 binds to the RNA polymerase "i" and "i+1" sites and prevents the binding of initiating nucleotides. eLife, 3, e02450.

Degen, D., Feng, Y., Zhang, Y., Ebright, K., Ebright, Y., Gigliotti, M., Vahedian-Movahed, H., Mandal, S., Talaue, M., Connell, N., Arnold, E., Fenical, W., and Ebright, R. (2014) Transcription inhibition by the depsipeptide antibiotic salinamide A. eLife, 3, e02451.

Vvedenskaya, I., Vahedian-Movahed, H., Bird, J., Knoblauch, J., Goldman, S., Zhang, Y., Ebright, R., and Nickels, B. (2014) Interactions between RNA polymerase and the "core recognition element" counteract pausing. Science 344, 1285-1289.

Ebright, R. (2014) Arylpropionyl-alpha-pyrone antibacterial agents. US Patent US8,772,332.

Tang, W., Liu, S, Degen, D., Ebright, R., and Prusov, E., (2014) Synthesis and evaluation of novel analogues of ripostatins. Chem. Eur. J. 20, 12310-12319.

Chakraborty, A., Mazumder, A., Lin, M., Hasemeyer, A., Xu, Q., Wang, D., Ebright, Y., and Ebright, R. (2015) Site‑specific incorporation of probes into RNA polymerase by unnatural-amino-acid mutagenesis and Staudinger-Bertozzi ligation. Meths. Mol. Biol. 1276, 101-131.

Hassan, H., Degen, D., Jang K., Ebright, R., and Fenical, W. (2015) Salinamide F, New depsipeptide antibiotic and inhibitor of bacterial RNA polymerase from a marine-derived Streptomyces sp. J. Antibiot. 68, 206-209.

Ebright, R., Degen, D., and Ebright, K.  (2015) Bridge-helix cap: target and method for inhibition of bacterial RNA polymerase. US Patent 9060970.

Feng, Y., Degen, D., Wang, X., Gigliotti, M., Liu, S., Zhang, Y., Das, D., Michalchuk, T., Ebright, Y., Talaue, M., Connell, N., and Ebright, R. (2015) Structural basis of transcription inhibition by CBR hydroxamidines and CBR pyrazoles. Structure 23, 1470-1481.

Ebright, R. and Ebright, Y. (2015) Antibacterial agents: high-potency myxopyronin derivatives. US Patent 9133155.

Vvedenskaya, I., Zhang, Y., Goldman, S., Valenti, A., Visone, V., Taylor, D., Ebright, R., and Nickels, B. (2015) Massively systematic transcript end readout (MASTER): transcription start site selection and transcriptional slippage. Molecular Cell 60, 953-965.

Ebright, R. and Ebright, Y. (2015) Antibacterial agents: side-chain-fluorinated myxopyronin derivatives. US Patent 9187446.

Ebright, R., Ebright, Y., Feng, Y., and Degen, D. (2015) Antibacterial agents: salinamide derivatives. US Patent 9221880.

Ebright, R., Zhang, Y., Degen, D., and Ebright, Y. (2016) Bipartite inhibitors of bacterial RNA polymerase: Sal-target-inhibitor/nucleoside-analog-inhibitor conjugates. US Patent 9243039.

Winkelman, J, Vvedenskaya, I., Zhang, Y., Zhang, Y., Bird, J., Taylor, D., Gourse, R., Ebright, R., and Nickels, B. (2016) Multiplexed protein-DNA crosslinking: scrunching in transcription start site selection. Science 351, 1090-1093.

Ebright, R., Ebright, Y., Shen, J., Bacci, J., Hiebel, A.-C., Solvible, W., Self, C., and Olson, G. (2016) Antibacterial agents: aryl myxopyronin derivatives. US Patent 9315495.

Vvedenskaya, I., Vahedian-Movahed, H., Zhang, Y., Taylor, D., Ebright, R., and Nickels, B. (2016) Interactions between RNA polymerase and the "core recognition element" are a determinant of transcription start site selection. Proc. Natl. Acad. Sci. USA 113, E2899-E2905.

Feng, Y., Zhang, Y., and Ebright, R. (2016) Structural basis of transcription activation. Science 352, 1330‑1333.

Bird, J., Zhang, Y., Tian, Y., Greene, L., Liu, M., Buckley, B., Krasny, L., Lee, J., Kaplan, C., Ebright, R., and Nickels, B. (2016) The mechanism of RNA 5' capping with NAD+, NADH, and desphosphoCoA. Nature 535, 444-447.

Ebright, R., Degen, D., Zhang, Y., Ebright, Y.  (2016) Bipartite inhibitors of bacterial RNA polymerase. US Patent 9415112.

Ebright, R. and Shen, J. (2016) Antibacterial agents: phloroglucinol derivatives. US Patent 9517994.

Ebright, R., Ebright, Y., Shen, J., Bacci, J., Hiebel, A.-C., Solvible, W., Self, C., and Olson, G. (2017) Antibacterial agents: aryl myxopyronin derivatives. US Patent 9592221.

Ebright, R., Ebright, Y., Feng, Y., and Degen, D. (2017) Antibacterial agents: salinamide derivatives.  US Patent 9605028.

Walker, S, Degen, D., Nickbarg, E., Carr, D., Soriano, A., Mandal, M., Painter, R., Sheth, P., Xiao, Li., Sher, X., Murgolo, N., Su, J., Olsen, D., Ebright, R., and Young, K. (2017) Affinity selection-mass spectrometry identifies a novel antibacterial RNA polymerase inhibitor.   ACS Chem. Biol. 12, 1346-1352.

Lin, W., Mandal, S., Degen, D., Liu, Y.., Ebright, Y., Li, S., Feng, Y., Zhang, Y., Mandal, S., Jiang, Y., Liu, S., Gigliotti, M., Talaue, M., Connell, N., Das, K., Arnold, E., and Ebright, R. (2017) Structural basis of Mycobacterium tuberculosis transcription and transcription inhibition. Mol. Cell 166, 169-179.

Maffioli, S., Zhang, Y., Degen, D., Carzaniga, T., Del Gatto, G., Serina, S., Monciardini, P., Mazzetti, C., Guglierame, P., Candiani, G., Chiriac, A.I., Facchetti, G., Kaltofen, P., Sahl, H.-G., Dehò, G., Donadio, S., and Ebright, R. (2017) Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase. Cell 169, 1240-1248.

Bird, J., Nickels, B., and Ebright, R. (2017) RNA capping by transcription initiation with non-canonical initiating nucleotides (NCINs): determination of relative efficiencies of transcription initiation with NCINs and NTPs. Bio-Protocol 7, e2336.

Boucher, H., Ambrose, P., Chambers, H., Ebright, R., Jezek, A., Murray, B., Newland, J., Ostrowsky, B., and Rex, J. (2017) Developing antimicrobial drugs for resistant pathogens and unmet needs. J. Infect. Dis. 216, 228-236.

Ebright, R., Ebright, Y., Feng, Y., and Degen, D. (2017) Antibacterial agents: salinamide derivatives. US Patent 9809626.

Ebright, R.  (2017) Antibacterial agents: combination of a rifamycin and a switch region inhibitor. US Patent 9839634.

Yu, L., Winkelman, J., Pukhrambam, C., Strick, T., Nickels, B., and Ebright, R. (2017) The mechanism of transcription start site selection. eLife 6, e32038.

Boucher, H., Ambrose, P., Chambers, H., Ebright, R., Jezek, A., Murray, B., Ostrowsky, B., Rex, J. (2017) Reply to Paul and Leibovici J. Infect. Dis. 217, 509-551.

Ebright, R., Ebright, Y., Mandal, S., Wilde, R., and Li, S. (2018) Antibacterial agents: N(alpha)-aroyl-N-aryl-phenylalaninamides. US Patent 9919998.

Ebright, R. (2018) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. US Patent 9945051.

Lin, W., Das, K., Degen, D., Mazumder, A., Duchi, D., Wang, D., Ebright, Y., Ebright, R.Y., Sineva, E., Gigliotti, M., Mandal, S., Jiang, Y., Liu, Y., Yin, R., Zhang, Z., Eng, E., Thomas, D., Donadio, S., Zhang, C., Kapanidis, A., and Ebright, R. (2018) Structural basis of transcription inhibition by fidaxomicin (lipiarmycin A3). Mol. Cell 70, 60-71.

Bird, J., Vvedenskaya, I., Zhang, Y., Zhang, Y., Jiao, X., Krasny, L., Kiledjian, M., Taylor, D., Ebright, R., and Nickels, B. (2018) CapZyme-Seq" comprehensively defines promoter-sequence determinants for RNA 5' capping with NAD+. Mol. Cell 70, 553-564.

Sosio, M., Gaspari, E., Iorio, M., Pessina, S., Medema, M., Bernasconi, A,. Simone, M., Maffioli, S., Ebright, R., and Donadio, S. (2018) Analysis of the pseudouridimycin biosynthetic pathway provides insights into the formation of C-nucleoside antibiotics. Cell Chem. Biol. 25, 540-549.

Ebright, R., Degen, D., Zhang, Y., Ebright, Y.  (2018) Bipartite inhibitors of bacterial RNA polymerase. US Patent 10010619.

Ebright, R., Ebright, Y., Shen, J., Bacci, J., Hiebel, A.-C., Solvible, W., Self, C., and Olson, G.  (2018) Antibacterial agents: aryl myxopyronin derivatives. European Patent 2861570.

Gabizon, R., Lee, A., Vahedian-Movahed, H., Ebright, R.H., and Bustamante, C. (2018) Pause sequences facilitate entry into long-lived paused states by reducing RNA polymerase transcription rates. Nature Comm. 9, 2930.

Duchi, D., Mazumder, A., Malinen, A., Ebright, R., and Kapanidis, A. (2018) The RNA polymerase clamp interconverts dynamically among three states and is stabilized in a partly closed state by ppGpp. Nucl. Acids Res. 14, 7284-7295.

Bird, J., Basu, U., Kuster, D., Ramachandran, A., Grudzien-Nogalska, E., Kiledjian, M., Temiakov, D., Patel, S., Ebright, R.H. and Nickels, B. (2018) Mitochondrial RNA capping: highly efficient 5'-RNA capping with NAD+ and NADH by yeast and human mitochondrial RNA polymerase. eLife, 7, e42179

Maffioli, S., Sosio, M., Ebright, R.H. and Donadio, S. (2018) Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside analog inhibitor of bacterial RNA polymerase. J. Indust. Microbiol. Technol. 46, 335-343.

Lin, W., Mandal, S., Degen, D., Cho, M., Feng, Y., Das, K., and Ebright, R.H. (2019) Structural basis of ECF-s-factor-dependent transcription initiation. Nature Commun. 10, 710.

Panduwawala, T., Iqbal, S., Thompson, A., Christensen, K., Genov, M., Pretsch, A., Pretsch, D., Liu, S., Ebright, R.H., Howells, A., Maxwell, A., and Moloney, M. (2019) Functionalised bicyclic tetramates derived from cysteine as antibacterial agents. Org. Biomol. Chem. 17, 5615-5632.

Talbot, G., Jezek, A., Murray, B., Jones, R., Ebright, R.H., Nau, G., Rodvold, K., Newland, J., and Boucher, H. (2019) The Infectious Diseases Society of America’s 10 × ’20 initiative (ten new systemic antibacterial agents FDA-approved by 2020). Clin. Infect. Dis. 69, 1-11.

Yin, Z., Kaelber, J., and Ebright, R.H. (2019) Structural basis of Q-dependent antitermination. Proc. Natl. Acad. Sci. USA 116, 18384-18390.

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