Crystal structure of substrate complexes of methylmalonyl-CoA mutase

X-ray crystal structures of methylmalonyl-CoA mutase in complexes with subs trate methylmalonyl-CoA and inhibitors 2-carboxypropyl-CoA and 3-carboxypro pyl-CoA (substrate and product analogues) show that the enzyme-substrate in teractions change little during the course of the rearrangement reaction, i n contrast to the large conformational change on substrate binding. The sub strate complex shows a 5'-deoxyadenine molecule in the active site, bound w eakly and not attached to the cobalt atom of coenzyme B-12, rotated and shi fted from its position in the substrate-free adenosylcobalamin complex. The position of Tyr alpha 89 close to the substrate explains the stereochemica l selectivity of the enzyme for (2R)-methylmalonyl-CoA.