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6th2

From Proteopedia

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Current revision

Crystal structure of Mycobacterium smegmatis CoaB in complex with CTP

Structural highlights

6th2 is a 4 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.844Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

COABC_MYCS2 Catalyzes two sequential steps in the biosynthesis of coenzyme A. In the first step cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine. In the second step the latter compound is decarboxylated to form 4'-phosphopantotheine.[HAMAP-Rule:MF_02225]

Publication Abstract from PubMed

Coenzyme A (CoA) is a fundamental co-factor for all life, involved in numerous metabolic pathways and cellular processes, and its biosynthetic pathway has raised substantial interest as a drug target against multiple pathogens including Mycobacterium tuberculosis. The biosynthesis of CoA is performed in five steps, with the second and third steps being catalysed in the vast majority of prokaryotes, including M. tuberculosis, by a single bifunctional protein, CoaBC. Depletion of CoaBC was found to be bactericidal in M. tuberculosis. Here we report the first structure of a full-length CoaBC, from the model organism Mycobacterium smegmatis, describe how it is organised as a dodecamer and regulated by CoA thioesters. A high-throughput biochemical screen focusing on CoaB identified two inhibitors with different chemical scaffolds. Hit expansion led to the discovery of potent and selective inhibitors of M. tuberculosis CoaB, which we show to bind to a cryptic allosteric site within CoaB.

Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site.,Mendes V, Green SR, Evans JC, Hess J, Blaszczyk M, Spry C, Bryant O, Cory-Wright J, Chan DS, Torres PHM, Wang Z, Nahiyaan N, O'Neill S, Damerow S, Post J, Bayliss T, Lynch SL, Coyne AG, Ray PC, Abell C, Rhee KY, Boshoff HIM, Barry CE 3rd, Mizrahi V, Wyatt PG, Blundell TL Nat Commun. 2021 Jan 8;12(1):143. doi: 10.1038/s41467-020-20224-x. PMID:33420031^[1]

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

References

↑ Mendes V, Green SR, Evans JC, Hess J, Blaszczyk M, Spry C, Bryant O, Cory-Wright J, Chan DS, Torres PHM, Wang Z, Nahiyaan N, O'Neill S, Damerow S, Post J, Bayliss T, Lynch SL, Coyne AG, Ray PC, Abell C, Rhee KY, Boshoff HIM, Barry CE 3rd, Mizrahi V, Wyatt PG, Blundell TL. Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site. Nat Commun. 2021 Jan 8;12(1):143. doi: 10.1038/s41467-020-20224-x. PMID:33420031 doi:http://dx.doi.org/10.1038/s41467-020-20224-x

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/6th2"

@@ Line 3: / Line 3: @@
 <StructureSection load='6th2' size='340' side='right'caption='[[6th2]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6th2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TH2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TH2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6th2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TH2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.844&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">coaBC, MSMEG_3054 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></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=6th2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6th2 OCA], [http://pdbe.org/6th2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6th2 RCSB], [http://www.ebi.ac.uk/pdbsum/6th2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6th2 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6th2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6th2 OCA], [https://pdbe.org/6th2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6th2 RCSB], [https://www.ebi.ac.uk/pdbsum/6th2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6th2 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/COABC_MYCS2 COABC_MYCS2] Catalyzes two sequential steps in the biosynthesis of coenzyme A. In the first step cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine. In the second step the latter compound is decarboxylated to form 4'-phosphopantotheine.[HAMAP-Rule:MF_02225]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Mycs2]]
+[[Category: Mycolicibacterium smegmatis MC2 155]]
-[[Category: Blaszczyk, M]]
+[[Category: Blaszczyk M]]
-[[Category: Blundell, T L]]
+[[Category: Blundell TL]]
-[[Category: Bryant, O]]
+[[Category: Bryant O]]
-[[Category: Cory-Wright, J]]
+[[Category: Cory-Wright J]]
-[[Category: Mendes, V]]
+[[Category: Mendes V]]
-[[Category: Bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate-cysteine ligase]]
-[[Category: Coabc]]
-[[Category: Ligase]]
-[[Category: Phosphopantothenate-cysteine ligase]]
-[[Category: Phosphopantothenoylcysteine decarboxylase]]
-[[Category: Phosphopantothenoylcysteine synthetase]]

6th2

From Proteopedia

Current revision

Crystal structure of Mycobacterium smegmatis CoaB in complex with CTP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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