On the Importance of Ribose Orientation in the Substrate Activation of the Coenzyme B12‐Dependent Mutases

Abstract

The degree to which the corrin ring portion of coenzyme B(12) can facilitate the H-atom-abstraction step in the glutamate mutase (GM)-catalyzed reaction of (S)-glutamate has been investigated with density functional theory. The crystal structure of GM identifies two possible orientations of the ribose portion of coenzyme B(12). In one orientation (A), the OH groups of the ribose extend away from the corrin ring, whereas in the other orientation (B) the OH groups, especially that involving O3', are instead directed towards the corrin ring. Our calculations identify a sizable stabilization amounting to about 30 kJ mol(-1) in the transition structure (TS) complex corresponding to orientation B (TS(B)CorIm). In the TS complex where the ribose instead is positioned in orientation A, no such effect is manifested. The observed stabilization in TS(B)CorIm appears to be the result of favorable interactions involving O3' and the corrin ring, including a C-HO hydrogen bond. We find that the degree of stabilization is not particularly sensitive to the Co-C distance. Our calculations show that any potential stabilization afforded to the H-atom-abstraction step by coenzyme B(12) is sensitive to the orientation of the ribose moiety.