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

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

173 Scopus citations

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.

Original language	English (US)
Pages (from-to)	541-552
Number of pages	12
Journal	Cell
Volume	122
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2005.07.017
State	Published - Aug 16 2005

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2005.07.017

Cite this

Tuske, S., Sarafianos, S. G., Wang, X., Hudson, B., Sineva, E., Mukhopadhyay, J., Birktoft, J. J., Leroy, O., Ismail, S., Clark, A. D., Dharia, C., Napoli, A., Laptenko, O., Lee, J., Borukhov, S., Ebright, R. H., & Arnold, E. (2005). Inhibition of bacterial RNA polymerase by streptolydigin: Stabilization of a straight-bridge-helix active-center conformation. Cell, 122(4), 541-552. https://doi.org/10.1016/j.cell.2005.07.017

@article{608b142d09c64ec691706059868ded08,

title = "Inhibition of bacterial RNA polymerase by streptolydigin: Stabilization of a straight-bridge-helix active-center conformation",

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.",

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

note = "Funding Information: We thank E. Steinbrecher and Pharmacia & Upjohn, Inc., for streptolydigin; J. Fralick and R. Landick for bacterial strains; staff members at BNLS and CHESS and S. Ginell at APS for assistance with synchrotron data collection; and H. Berman, K. Das, J. Ding, C. Lawson, J. Patel, and members of our laboratories for assistance and discussions. This work was supported by NIH grants GM41376 (to R.H.E.), AI27690 and GM66671 (to E.A.), GM54098 (to S.B.), and GM21589 (to H. Berman; supported A.N.) and by a Howard Hughes Medical Investigatorship (to R.H.E.). ",

year = "2005",

month = aug,

day = "16",

doi = "10.1016/j.cell.2005.07.017",

language = "English (US)",

volume = "122",

pages = "541--552",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "4",

}

Tuske, S, Sarafianos, SG, Wang, X, Hudson, B, Sineva, E, Mukhopadhyay, J, Birktoft, JJ, Leroy, O, Ismail, S, Clark, AD, Dharia, C, Napoli, A, Laptenko, O, Lee, J, Borukhov, S, Ebright, RH & Arnold, E 2005, 'Inhibition of bacterial RNA polymerase by streptolydigin: Stabilization of a straight-bridge-helix active-center conformation', Cell, vol. 122, no. 4, pp. 541-552. https://doi.org/10.1016/j.cell.2005.07.017

TY - JOUR

T1 - Inhibition of bacterial RNA polymerase by streptolydigin

T2 - Stabilization of a straight-bridge-helix active-center conformation

AU - Tuske, Steven

AU - Sarafianos, Stefan G.

AU - Wang, Xinyue

AU - Hudson, Brian

AU - Sineva, Elena

AU - Mukhopadhyay, Jayanta

AU - Birktoft, Jens J.

AU - Leroy, Olivier

AU - Ismail, Sajida

AU - Clark, Arthur D.

AU - Dharia, Chhaya

AU - Napoli, Andrew

AU - Laptenko, Oleg

AU - Lee, Jookyung

AU - Borukhov, Sergei

AU - Ebright, Richard H.

AU - Arnold, Eddy

N1 - Funding Information: We thank E. Steinbrecher and Pharmacia & Upjohn, Inc., for streptolydigin; J. Fralick and R. Landick for bacterial strains; staff members at BNLS and CHESS and S. Ginell at APS for assistance with synchrotron data collection; and H. Berman, K. Das, J. Ding, C. Lawson, J. Patel, and members of our laboratories for assistance and discussions. This work was supported by NIH grants GM41376 (to R.H.E.), AI27690 and GM66671 (to E.A.), GM54098 (to S.B.), and GM21589 (to H. Berman; supported A.N.) and by a Howard Hughes Medical Investigatorship (to R.H.E.).

PY - 2005/8/16

Y1 - 2005/8/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=23944521364&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23944521364&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2005.07.017

DO - 10.1016/j.cell.2005.07.017

M3 - Article

C2 - 16122422

AN - SCOPUS:23944521364

SN - 0092-8674

VL - 122

SP - 541

EP - 552

JO - Cell

JF - Cell

IS - 4

ER -

Inhibition of bacterial RNA polymerase by streptolydigin: Stabilization of a straight-bridge-helix active-center conformation

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this