On the mechanism of dimethylarginine dimethylaminohydrolase inactivation by 4-halopyridines.

ABSTRACT: Small molecules capable of selective covalent protein modification are of significant interest for the development of biological probes and therapeutics. We recently reported that 2-methyl-4-bromopyridine is a quiescent affinity label for the nitric oxide controlling enzyme dimethylarginine dimethylaminohydrolase (DDAH) (Johnson, C. M.; Linsky, T. W.; Yoon, D. W.; Person, M. D.; Fast, W. J. Am. Chem. Soc. 2011, 133, 1553-1562). Discovery of this novel protein modifier raised the possibility that the 4-halopyridine motif may be suitable for wider application. Therefore, the inactivation mechanism of the related compound 2-hydroxymethyl-4-chloropyridine is probed here in more detail. Solution studies support an inactivation mechanism in which the active site Asp66 residue stabilizes the pyri

SUBMITTER: Johnson CM 

PROVIDER: S-EPMC3135753 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature