Solution structure, enzymatic, and non-enzymatic reactivity of 3-isoadenosylcobalamin, a structural isomer of coenzyme B12 with surprising coenzymic activity

Homoadenosylcobalamins as probes for exploring the active sites of coenzyme B12‐dependent diol dehydratase and ethanolamine ammonia‐lyase

“…For Aristeromycylcobalamin (AdoCbl analogue in which the ribosyl oxygen atom is replaced by ‐CH 2 ‐) is 36–44% and 38% as active as AdoCbl in diol dehydratase [27,43,44] and glycerol dehydratase [44], respectively, but it serves as a strong competitive inhibitor for ethanolamine ammonia‐lyase [44] and ribonucleotide reductase [29] and a weak competitive inhibitor for methylmalonyl‐CoA mutase [44]. 2′‐DeoxyAdoCbl is 31%, 17%, and 5–13% as active as AdoCbl for diol dehydratase [38,45], glycerol dehydratase [41], and ribonucleotide reductase [29,35], respectively, but shows only 1–2% activity for methylmalonyl‐CoA mutase [46] or no activity for glutamate mutase [45]. Two series of AdoCbl analogues are of special interest.…”

“…To elucidate the mechanism of enzymatic activation (labilization) of the coenzyme Co‐C bond, the structure–function relationship of AdoCbl and the role of each structural component of the coenzyme were extensively studied using various coenzyme analogues [24,29,33–35]. Coenzyme analogues, in which one of the structural components of the coenzyme is substituted by a closely related group, were synthesized and examined for coenzymic activity and binding affinity for the enzyme.…”

“…Glycerol dehydratase shows similar specificity for the adenosyl group [39–42]. In ribonucleotide reductase [24,29,35], the interaction at N3 of adenine is essential but interaction at 6‐NH 2 is less important than those in diol dehydratase. Ribonucleotide reductase shows more strict specificity for the ribose moiety than diol dehydratase.…”

Chemistry and Enzymology of Vitamin B12

“…A second interesting difference between the Class I and Class II enzymes is the specificity for AdoCbl. The Class II enzymes are remarkably promiscuous in tolerating structural variations in the coenzyme …”

“…The Class II enzymes are remarkably promiscuous in tolerating structural variations in the coenzyme. 243 Many coenzyme analogues with structural alterations in the adenine and its ribose, the corrin ring and its substituents, and the axial nucleotide are partially active coenzymes for the Class II enzymes (although some are inactive inhibitors). In contrast, the Class I mutases are much more specific for AdoCbl itself.…”