5mwo

From Proteopedia

(Difference between revisions)

Revision as of 07:31, 19 August 2020

Structure of Mycobacterium Tuberculosis Transcriptional Regulatory Repressor Protein (EthR) in complex with fragment 7E8.

Structural highlights

5mwo is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ETHR_MYCTU] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).^[1] ^[2]

Publication Abstract from PubMed

Native nanoelectrospray ionization mass spectrometry is an underutilized technique for fragment screening. In this study, the first demonstration is provided of the use of native mass spectrometry for screening fragments against a protein-DNA interaction. EthR is a transcriptional repressor of EthA expression in Mycobacterium tuberculosis (Mtb) that reduces the efficacy of ethionamide, a second-line antitubercular drug used to combat multidrug-resistant Mtb strains. A small-scale fragment screening campaign was conducted against the EthR-DNA interaction using native mass spectrometry, and the results were compared with those from differential scanning fluorimetry, a commonly used primary screening technique. Hits were validated by surface plasmon resonance and X-ray crystallography. The screening campaign identified two new fragments that disrupt the EthR-DNA interaction in vitro (IC50 =460-610 mum) and bind to the hydrophobic channel of the EthR dimer.

Fragment Screening against the EthR-DNA Interaction by Native Mass Spectrometry.,Chan DS, Mendes V, Thomas SE, McConnell BN, Matak-Vinkovic D, Coyne AG, Blundell TL, Abell C Angew Chem Int Ed Engl. 2017 Jun 19;56(26):7488-7491. doi:, 10.1002/anie.201702888. Epub 2017 May 31. PMID:28513917^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Baulard AR, Betts JC, Engohang-Ndong J, Quan S, McAdam RA, Brennan PJ, Locht C, Besra GS. Activation of the pro-drug ethionamide is regulated in mycobacteria. J Biol Chem. 2000 Sep 8;275(36):28326-31. PMID:10869356 doi:10.1074/jbc.M003744200
↑ DeBarber AE, Mdluli K, Bosman M, Bekker LG, Barry CE 3rd. Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9677-82. PMID:10944230
↑ Chan DS, Mendes V, Thomas SE, McConnell BN, Matak-Vinkovic D, Coyne AG, Blundell TL, Abell C. Fragment Screening against the EthR-DNA Interaction by Native Mass Spectrometry. Angew Chem Int Ed Engl. 2017 Jun 19;56(26):7488-7491. doi:, 10.1002/anie.201702888. Epub 2017 May 31. PMID:28513917 doi:http://dx.doi.org/10.1002/anie.201702888

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mwo"

@@ Line 1: / Line 1: @@
 ==Structure of Mycobacterium Tuberculosis Transcriptional Regulatory Repressor Protein (EthR) in complex with fragment 7E8.==
-<StructureSection load='5mwo' size='340' side='right' caption='[[5mwo]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
+<StructureSection load='5mwo' size='340' side='right'caption='[[5mwo]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mwo]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MWO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mwo]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MWO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MWO FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=J6W:(5-methyl-1-benzothiophen-2-yl)methanol'>J6W</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=J6W:(5-methyl-1-benzothiophen-2-yl)methanol'>J6W</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5mwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mwo OCA], [http://pdbe.org/5mwo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mwo RCSB], [http://www.ebi.ac.uk/pdbsum/5mwo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mwo ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mwo OCA], [http://pdbe.org/5mwo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mwo RCSB], [http://www.ebi.ac.uk/pdbsum/5mwo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mwo ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Abell, C]]
 [[Category: Blundell, T L]]

5mwo

From Proteopedia

Revision as of 07:31, 19 August 2020

Structure of Mycobacterium Tuberculosis Transcriptional Regulatory Repressor Protein (EthR) in complex with fragment 7E8.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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