Perspective on the Structural Basis for Human Aldo-Keto Reductase 1B10 Inhibition.

ABSTRACT: Human aldo-keto reductase 1B10 (AKR1B10) is overexpressed in many cancer types and is involved in chemoresistance. This makes AKR1B10 to be an interesting drug target and thus many enzyme inhibitors have been investigated. High-resolution crystallographic structures of AKR1B10 with various reversible inhibitors were deeply analyzed and compared to those of analogous complexes with aldose reductase (AR). In both enzymes, the active site included an anion-binding pocket and, in some cases, inhibitor binding caused the opening of a transient specificity pocket. Different structural conformers were revealed upon inhibitor binding, emphasizing the importance of the highly variable loops, which participate in the transient opening of additional binding subpockets. Two key differences between AKR

SUBMITTER: Ruiz FX 

PROVIDER: S-EPMC8708191 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature