5cjv

Isobutyryl-CoA mutase fused with bound adenosylcobalamin, GDP, Mg (holo-IcmF/GDP), and substrate isovaleryl-coenzyme A

spinqualitylabelsall models 5cjv, resolution 3.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cjv is a 2 chain structure with sequence from Cupriavidus metallidurans CH34. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.45Å Ligands: 5AD, B12, GDP, IVC, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ICMF_CUPMC Catalyzes the reversible interconversion of isobutyryl-CoA and n-butyryl-CoA, and to a much lesser extent, of pivalyl-CoA and isovaleryl-CoA, using radical chemistry (PubMed:22167181). Also exhibits GTPase activity, associated with its G-protein domain (MeaI) that functions as a chaperone that assists cofactor delivery and proper holo-enzyme assembly (PubMed:22167181, PubMed:25675500). The G-domain of IcmF has also a role in its cofactor repair (PubMed:28130442). Does not display ATPase activity. Publication Abstract from PubMed Acyl-CoA mutases are a growing class of adenosylcobalamin-dependent radical enzymes that perform challenging carbon skeleton rearrangements in primary and secondary metabolism. Members of this class of enzymes must precisely control substrate positioning to prevent oxidative interception of radical intermediates during catalysis. Our understanding of substrate specificity and catalysis in acyl-CoA mutases, however, is incomplete. Here, we present crystal structures of IcmF, a natural fusion protein variant of isobutyryl-CoA mutase, in complex with the adenosylcobalamin cofactor and four different acyl-CoA substrates. These structures demonstrate how the active site is designed to accommodate the aliphatic acyl chains of each substrate. The structures suggest that a conformational change of the 5'-deoxyadenosyl group from C2'-endo to C3'-endo could contribute to initiation of catalysis. Furthermore, detailed bioinformatic analyses guided by our structural findings identify critical determinants of acyl-CoA mutase substrate specificity and predict new acyl-CoA mutase-catalyzed reactions. These results expand our understanding of substrate specificity and catalytic scope of acyl-CoA mutases and could benefit engineering efforts for biotechnological applications ranging from production of biofuels and commercial products to hydrocarbon remediation. Structural Basis for Substrate Specificity in Adenosylcobalamin-Dependent Isobutyryl-CoA Mutase and Related Acyl-CoA Mutases.,Jost M, Born DA, Cracan V, Banerjee R, Drennan CL J Biol Chem. 2015 Aug 28. pii: jbc.M115.676890. PMID:26318610 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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