Format

Send to

Choose Destination
Curr Opin Struct Biol. 2009 Dec;19(6):715-23. doi: 10.1016/j.sbi.2009.10.010. Epub 2009 Nov 18.

Structures of RNA polymerase-antibiotic complexes.

Author information

1
Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA.

Abstract

Inhibition of bacterial RNA polymerase (RNAP) is an established strategy for antituberculosis therapy and broad-spectrum antibacterial therapy. Crystal structures of RNAP-inhibitor complexes are available for four classes of antibiotics: rifamycins, sorangicin, streptolydigin, and myxopyronin. The structures define three different targets, and three different mechanisms, for inhibition of bacterial RNAP: (1) rifamycins and sorangicin bind near the RNAP active center and block extension of RNA products; (2) streptolydigin interacts with a target that overlaps the RNAP active center and inhibits conformational cycling of the RNAP active center; and (3) myxopyronin interacts with a target remote from the RNAP active center and functions by interfering with opening of the RNAP active-center cleft to permit entry and unwinding of DNA and/or by interfering with interactions between RNAP and the DNA template strand. The structures enable construction of homology models of pathogen RNAP-antibiotic complexes, enable in silico screening for new antibacterial agents, and enable rational design of improved antibacterial agents.

PMID:
19926275
PMCID:
PMC2950656
DOI:
10.1016/j.sbi.2009.10.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center