Crystal structure of substrate complexes of methylmalonyl-CoA mutase.
X-ray crystal structures of methylmalonyl-CoA mutase in complexes with substrate methylmalonyl-CoA and inhibitors 2-carboxypropyl-CoA and 3-carboxypropyl-CoA (substrate and product analogues) show that the enzyme-substrate interactions change little during the course of the rearrangement reaction, in contrast to the large conformational change on substrate binding. The substrate complex shows a 5'-deoxyadenine molecule in the active site, bound weakly and not attached to the cobalt atom of coenzyme B12, rotated and shifted from its position in the substrate-free adenosylcobalamin complex. The position of Tyralpha89 close to the substrate explains the stereochemical selectivity of the enzyme for (2R)-methylmalonyl-CoA.
Mancia
F
F
MRC Laboratory of Molecular Biology, Cambridge, UK.
Smith
G A
GA
Evans
P R
PR
D001665:Binding Sites; D002384:Catalysis; D003065:Coenzyme A / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D003839:Deoxyadenosines / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry; D007527:Isoenzymes / Q000737:chemistry; D046911:Macromolecular Substances; D008765:Methylmalonyl-CoA Mutase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011424:Propionibacterium / Q000201:enzymology; D013237:Stereoisomerism; D013379:Substrate Specificity
C090490:3-carboxypropyl-coenzyme A; D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D046911:Macromolecular Substances; C033714:5'-deoxyadenosine; D008765:Methylmalonyl-CoA Mutase; D003065:Coenzyme A