Multiple roles of ATP:cob(I)alamin adenosyltransferases in the conversion of B12 to coenzyme B12 |
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Authors: | Paola E Mera Jorge C Escalante-Semerena |
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Institution: | (1) Department of Developmental Biology, Stanford University, 279 Campus Drive, Stanford, CA 94305, USA;(2) Department of Bacteriology, University of Wisconsin, 1550 Linden Drive, Madison, WI 53706, USA; |
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Abstract: | Our mechanistic understanding of the conversion of vitamin B12 into coenzyme B12 (a.k.a. adenosylcobalamin, AdoCbl) has been substantially advanced in recent years. Insights into the multiple roles played
by ATP:cob(I)alamin adenosyltransferase (ACA) enzymes have emerged through the crystallographic, spectroscopic, biochemical,
and mutational analyses of wild-type and variant proteins. ACA enzymes circumvent the thermodynamic barrier posed by the very
low redox potential associated with the reduction of cob(II)alamin to cob(I)alamin by generating a unique four-coordinate
cob(II)alamin intermediate that is readily converted to cob(I)alamin by physiological reductants. ACA enzymes not only synthesize
AdoCbl but also they deliver it to the enzymes that use it, and in some cases, enzymes in which its function is needed to
maintain the fidelity of the AdoCbl delivery process have been identified. Advances in our understanding of ACA enzyme function
have provided valuable insights into the role of specific residues, and into why substitutions of these residues have profound
negative effects on human health. From an applied science standpoint, a better understanding of the adenosylation reaction
may lead to more efficient ways of synthesizing AdoCbl. |
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