Development of a high-throughput in vitro assay to identify selective inhibitors for human ALDH1A1.

ABSTRACT: The human aldehyde dehydrogenase (ALDH) superfamily consists of at least 19 enzymes that metabolize endogenous and exogenous aldehydes. Currently, there are no commercially available inhibitors that target ALDH1A1 but have little to no effect on the structurally and functionally similar ALDH2. Here we present the first human ALDH1A1 structure, as the apo-enzyme and in complex with its cofactor NADH to a resolution of 1.75 and 2.1Å, respectfully. Structural comparisons of the cofactor binding sites in ALDH1A1 with other closely related ALDH enzymes illustrate a high degree of similarity. In order to minimize discovery of compounds that inhibit both isoenzymes by interfering with their conserved cofactor binding sites, this study reports the use of an in vitro, NAD(+)-independent, esterase-b

SUBMITTER: Morgan CA 

PROVIDER: S-EPMC4414680 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature