A Base‐Off Analogue of Coenzyme‐B12 with a Modified Nucleotide Loop
Open Access
- 1 December 1997
- journal article
- Published by Wiley in European Journal of Biochemistry
- Vol. 250 (2) , 303-307
- https://doi.org/10.1111/j.1432-1033.1997.0303a.x
Abstract
(Coβ‐5′‐Deoxyadenosin‐5′‐yl)‐(p‐cresolyl)cobamide (Ado‐PCC), an analogue of the base‐off form of coenzyme‐B12 (CoB12), was prepared by alkylation of (Coα/β‐cyano/aqua)‐(p‐cresolyl)cobamide (PCC) with 5′‐chloro‐5′‐deoxyadenosine. The 500 MHz 1H‐NMR spectrum of Ado‐PCC in D2O at pH 7.4 was completely analyzed using COSY and NOESY two‐dimensional experiments. The coenzyme and inhibitory activities of Ado‐PCC were tested with three coenzyme‐B12‐dependent enzymes: (R)‐methylmalonyl‐CoA mutase, glycerol dehydratase, and diol dehydratase. Ado‐PCC showed strong coenzyme activity with methylmalonyl‐CoA mutase, which is known to bind the base‐off form of CoB12. In contrast, Ado‐PCC had no coenzyme activity but acted instead as a competitive inhibitor with glycerol dehydratase and diol dehydratase, which are likely to prefer the base‐on form of CoB12. These results indicate that Ado‐PCC, whose structure is analogous to the base‐off form of CoB12, can be used for probing the mode of coenzyme binding by coenzyme‐B12‐dependent enzymes.Keywords
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