Inhibition of Bacterial RNA Polymerase by Streptolydigin: Stabilization of a Straight-Bridge-Helix Active-Center Conformation

Steven Tuske; Stefan G Sarafianos; Xinyue Wang; Brian Hudson; Elena Sineva; Jayanta Mukhopadhyay; Jens J Birktoft; Olivier Leroy; Sajida Ismail; Arthur D Clark; Chhaya Dharia; Andrew Napoli; Oleg Laptenko; Jookyung Lee; Sergei Borukhov; Richard H Ebright; Eddy Arnold

doi:10.1016/j.cell.2005.07.017

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Inhibition of Bacterial RNA Polymerase by Streptolydigin: Stabilization of a Straight-Bridge-Helix Active-Center Conformation

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Inhibition of Bacterial RNA Polymerase by Streptolydigin: Stabilization of a Straight-Bridge-Helix Active-Center Conformation

Steven Tuske, Stefan G Sarafianos, Xinyue Wang, Brian Hudson, Elena Sineva, Jayanta Mukhopadhyay, Jens J Birktoft, Olivier Leroy, Sajida Ismail, Arthur D Clark, …

Cell, Vol.122(4), pp.541-552

08/26/2005

DOI: https://doi.org/10.1016/j.cell.2005.07.017

PMCID: PMC2754413

PMID: 16122422

Abstract

We define the target, mechanism, and structural basis of inhibition of bacterial RNA polymerase (RNAP) by the tetramic acid antibiotic streptolydigin (Stl). Stl binds to a site adjacent to but not overlapping the RNAP active center and stabilizes an RNAP-active-center conformational state with a straight-bridge helix. The results provide direct support for the proposals that alternative straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations exist and that cycling between straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations is required for RNAP function. The results set bounds on models for RNAP function and suggest strategies for design of novel antibacterial agents.

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Title: Inhibition of Bacterial RNA Polymerase by Streptolydigin: Stabilization of a Straight-Bridge-Helix Active-Center Conformation
Creators: Steven Tuske - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Stefan G Sarafianos - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Xinyue Wang - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Brian Hudson - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Elena Sineva - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Jayanta Mukhopadhyay - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Jens J Birktoft - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Olivier Leroy - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Sajida Ismail - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Arthur D Clark - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Chhaya Dharia - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Andrew Napoli - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Oleg Laptenko - Department of Cell Biology, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084
Jookyung Lee - Department of Cell Biology, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084
Sergei Borukhov - Department of Cell Biology, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084
Richard H Ebright - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Eddy Arnold - Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854
Publication Details: Cell, Vol.122(4), pp.541-552
Date published: 08/26/2005
Publisher: Elsevier Inc
Academic Unit: Waksman Institute of Microbiology; Center for Advanced Biotechnology and Medicine; Institute for Quantitative Biomedicine
Language: English
Resource Type: Journal article
Identifiers: 991031654729104646