Controlling the reactivity of radical intermediates by coenzyme B(12)-dependent methylmalonyl-CoA mutase.
Adenosylcobalamin or coenzyme B(12)-dependent enzymes are members of the still relatively small group of radical enzymes and catalyse 1,2-rearrangement reactions. A member of this family is methylmalonyl-CoA mutase, which catalyses the isomerization of methylmalonyl-CoA to succinyl-CoA and, unlike the others, is present in both bacteria and animals. Enzymes that catalyse some of the most chemically challenging reactions are the ones that tend to deploy radical chemistry. The use of radical intermediates in an active site lined with amino acid side chains that threaten to extinguish the reaction by presenting alternative groups for abstraction poses the conundrum of how the enzymes control their reactivity. In this review, insights into this issue that have emerged from kinetic, mutagenesis and structural studies are described for methylmalonyl-CoA mutase.
Biochemistry Department, University of Nebraska, Lincoln, NE 68588-0664, USA. rbanerjee1@unl.edu
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D000214:Acyl Coenzyme A / Q000378:metabolism; D001665:Binding Sites; D005609:Free Radicals / Q000378:metabolism; D007536:Isomerism; D008765:Methylmalonyl-CoA Mutase / Q000737:chemistry / Q000378:metabolism*; D016296:Mutagenesis; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*
D000214:Acyl Coenzyme A; D005609:Free Radicals; D011994:Recombinant Proteins; C015357:methylmalonyl-coenzyme A; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12