6oxd | pdb_00006oxd

Structure of Mycobacterium tuberculosis methylmalonyl-CoA mutase with adenosyl cobalamin

spinqualitylabelsall models 6oxd, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6oxd is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: 5AD, K, NJS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MUTB_MYCTU 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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