View source for 6oxd


==Structure of Mycobacterium tuberculosis methylmalonyl-CoA mutase with adenosyl cobalamin==
<StructureSection load='6oxd' size='340' side='right'caption='[[6oxd]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6oxd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OXD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5AD:5-DEOXYADENOSINE'>5AD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NJS:5-O-[(S)-{[(S)-[(3R)-4-({(3S)-3-[(2-{[(2Z)-3-carboxybut-2-enoyl]sulfanyl}ethyl)amino]-3-hydroxypropyl}amino)-3-hydroxy-2,2-dimethyl-4-oxobutoxy](hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl]adenosine+3-(dihydrogen+phosphate)'>NJS</scene></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=6oxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oxd OCA], [https://pdbe.org/6oxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oxd RCSB], [https://www.ebi.ac.uk/pdbsum/6oxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oxd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MUTB_MYCTU MUTB_MYCTU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Itaconate is an immunometabolite with both anti-inflammatory and bactericidal effects. Its coenzyme A (CoA) derivative, itaconyl-CoA, inhibits B12-dependent methylmalonyl-CoA mutase (MCM) by an unknown mechanism. We demonstrate that itaconyl-CoA is a suicide inactivator of human and Mycobacterium tuberculosis MCM, which forms a markedly air-stable biradical adduct with the 5'-deoxyadenosyl moiety of the B12 coenzyme. Termination of the catalytic cycle in this way impairs communication between MCM and its auxiliary repair proteins. Crystallography and spectroscopy of the inhibited enzyme are consistent with a metal-centered cobalt radical ~6 angstroms away from the tertiary carbon-centered radical and suggest a means of controlling radical trajectories during MCM catalysis. Mycobacterial MCM thus joins enzymes in the glyoxylate shunt and the methylcitrate cycle as targets of itaconate in pathogen propionate metabolism.

Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair.,Ruetz M, Campanello GC, Purchal M, Shen H, McDevitt L, Gouda H, Wakabayashi S, Zhu J, Rubin EJ, Warncke K, Mootha VK, Koutmos M, Banerjee R Science. 2019 Nov 1;366(6465):589-593. doi: 10.1126/science.aay0934. PMID:31672889<ref>PMID:31672889</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6oxd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Banerjee R]]
[[Category: Koutmos M]]
[[Category: Purchal M]]
[[Category: Ruetz M]]