Molecular basis of prodrug activation by human valacyclovirase, an alpha-amino acid ester hydrolase.

ABSTRACT: Chemical modification to improve biopharmaceutical properties, especially oral absorption and bioavailability, is a common strategy employed by pharmaceutical chemists. The approach often employs a simple structural modification and utilizes ubiquitous endogenous esterases as activation enzymes, although such enzymes are often unidentified. This report describes the crystal structure and specificity of a novel activating enzyme for valacyclovir and valganciclovir. Our structural insights show that human valacyclovirase has a unique binding mode and specificity for amino acid esters. Biochemical data demonstrate that the enzyme hydrolyzes esters of alpha-amino acids exclusively and displays a broad specificity spectrum for the aminoacyl moiety similar to tricorn-interacting aminopeptidase F

SUBMITTER: Lai L 

PROVIDER: S-EPMC2431032 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature