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Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition

Structural Basis of Mycobacterium tuberculosis Transcription and Transcription InhibitionMycobacterium 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.

Mol Cell. 2017 Apr 20;66(2):169-179.e8.
doi: 10.1016/j.molcel.2017.03.001.
Epub 2017 Apr 6.

 

© Copyright 2017 Elsevier Inc.

  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.

Another SBC Highlight:

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state
A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chain

 

Protein Sci. 2017 Apr;26(4):857-869.
doi: 10.1002/pro.3134. Epub 2017 Mar 6.

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Highlights featured by either ANL or APS

 

SBC Announcements:

 

19-ID Pilatus Detector

 

SBC has implemented a Pilatus 3 X 6M detector into the User Program at beamline 19-ID. Data collected by our users has been of outstanding quality.

 

 

19-BM Robotic sample mounter available

 

A robot is available for use at beamline 19-BM. The sample dewar accommodates ten Unipuck magazines; pins must be 18mm in length and use either SSRL or ALS bases. Experienced users may now request remote access to 19-BM when applying for beamtime.

 

 

SBC Staff Hosting Changes

 

SBC staff are now available for User Support between the hours of 8:00am and 10:pm.

 

 

 

ALSO: Please Be Aware...!

 

APS requests the Experimental Safety Approval Form (ESAF) be submitted at least seven days prior to your scheduled beamtime.

 

Failure to submit your ESAF in advance may result in delaying the beginning of your experiment.

 

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If you have any suggestions or comments, please feel free to e-mail us.

 

Rapid Access Beamtime Available:

SBC Beamtime Request System

The on-line SBC Beamtime Request System allows users to view available beamtime on 19-ID and 19-BM, and to submit a request for rapid beamtime allocation.

Beamtime is available to the research community via a peer reviewed proposal system; it is supported by the U.S. Department of Energy, Office of Biological and Environmental Research.

Current Beamline Statistics:

APS PDB Depositions from BioSync
SBC Sector 19 2015 2016 2017 TOTAL
ID BM ID BM ID BM
PDB Depositions 262 32 186 28 77 12 5034

APS Publications Database:

Publications Total
SBC-CAT Publication List: 19-ID 1508
SBC-CAT Publication List: 19-BM 532
SBC-CAT Publication List: ALL
APS Publications Database

MCSG / APCF Announcements:

 

The Midwest Center for Structural Genomics (MCSG) is accepting applications for access to the MCSG User Resource.

 

MCSG's structure determination platform is well established, and combines technologies, robotics and expertise for gene cloning, protein production, and crystallization, as well as biochemical and biophysical characterization.

 

For further information, please contact Andrzej Joachimiak.

 

Future Meetings:

 

2017 Annual Meeting of the American Crystallographic Association

May 26-30, 2017

New Orleans; Louisiana, USA

 

10th annual CCP4 crystallographic school “From data collection to structure refinement and beyond”

June 19-26, 2017

Argonne National Laboratory; Chicago; Illinois, USA

 

Protein Society's 31st Annual Symposium

July 24-27, 2017

Montreal; Quebec, Canada

 

SBC Beamline Phone Numbers:

Phone Location Number
19-ID Beamline Control Station 630-252-9823
19-ID Beamline Cordless Phone 630-252-0569
19-ID Beamline Inside D-Hutch 630-252-1819
 
19-BM Beamline Control Station 630-252-9833
19-BM Beamline Cordless Phone 630-252-0568
19-BM Beamline Inside D-Hutch 630-252-1719