Summary information and primary citation

PDB-id
5uh6; SNAP-derived features in text and JSON formats; DNAproDB
Class
transcription-DNA-RNA-antibiotic
Method
X-ray (3.837 Å)
Summary
Crystal structure of mycobacterium tuberculosis transcription initiation complex containing 2ntrna in complex with rifampin
Reference
Lin W, Mandal S, Degen D, Liu Y, Ebright YW, Li S, Feng Y, Zhang Y, Mandal S, Jiang Y, Liu S, Gigliotti M, Talaue M, Connell N, Das K, Arnold E, Ebright RH (2017): "Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition." Mol. Cell, 66, 169-179.e8. doi: 10.1016/j.molcel.2017.03.001.
Abstract
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. Mtb RNA polymerase (RNAP) is the target of the first-line antituberculosis drug rifampin (Rif). We report crystal structures of Mtb RNAP, alone and in complex with Rif, at 3.8-4.4 Å resolution. The results identify an Mtb-specific structural module of Mtb RNAP and establish that Rif functions by a steric-occlusion mechanism that prevents extension of RNA. We also report non-Rif-related compounds-Nα-aroyl-N-aryl-phenylalaninamides (AAPs)-that potently and selectively inhibit Mtb RNAP and Mtb growth, and we report crystal structures of Mtb RNAP in complex with AAPs. AAPs bind to a different site on Mtb RNAP than Rif, exhibit no cross-resistance with Rif, function additively when co-administered with Rif, and suppress resistance emergence when co-administered with Rif.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js