Structural Basis for the Activation of the Cobalt‐Carbon Bond and Control of the Adenosyl Radical in Coenzyme B12 Catalysis

Abstract

AbstractAdenosylcobalamin (AdoCbl), or coenzyme B12, is a naturally occurring organometallic compound that serves as a cofactor for enzymes that catalyze intramolecular group‐transfer reactions and ribonucleotide reduction in a wide variety of organisms from bacteria to animals. AdoCbl‐dependent enzymes are radical enzymes that generate an adenosyl radical by homolysis of the coenzyme's cobalt‐carbon (Co−C) bond for catalysis. How do the enzymes activate and cleave the Co−C bond to form the adenosyl radical? How do the enzymes utilize the high reactivity of the adenosyl radical for catalysis by suppressing undesirable side reactions? Our recent structural studies, which aimed to solve these problems with diol dehydratase and ethanolamine ammonia‐lyase, established the crucial importance of the steric strain of the Co−C bond and conformational stabilization of the adenosyl radical for coenzyme B12 catalysis. We outline here our results obtained with these eliminating isomerases and compare them with those obtained with other radical B12 enzymes.