Mirror “Base-off” Conformation of Coenzyme B12 in Human Adenosyltransferase and Its Downstream Target, Methylmalonyl-CoA Mutase
- 17 December 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 127 (2) , 526-527
- https://doi.org/10.1021/ja044365l
Abstract
Human adenosyltransferase synthesizes coenzyme B12, for the target mitochondrial B12 enzyme, methylmalonyl-CoA mutase. It binds B12 in the “base-off” conformation in both the Co2+ and Co3+ oxidation states as revealed by UV−visible and EPR spectroscopy although it lacks the signature DXHXXG motif found in other B12 proteins that bind the cofactor in this conformation. The “base-off” conformation, which is rare at physiological pH, mirrors that in the target enzyme, methylmalonyl-CoA mutase, which utilizes the product, AdoCbl. However, the coordination environment for cobalt in the two proteins is distinct, which is reflected in an ∼40-fold difference in their affinity for the cofactor.Keywords
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