Inhibitor-Dependent Usage of the S1' Specificity Pocket of ER Aminopeptidase 2.

ABSTRACT: Endoplasmic reticulum aminopeptidase 2 (ERAP2) is an intracellular enzyme involved in the processing of antigenic peptides intended for presentation by major histocompatibility complex class I (MHCI) molecules. Because of its role in regulating immune responses, ERAP2 is an emerging pharmacological target. Phosphinic pseudopeptides are potent transition-state analogue inhibitors of ERAP2. Previous structure-activity studies have revealed a complex but ambiguous relationship between the occupation of putative specificity pockets and the inhibitor efficacy. To address these problems, we solved crystal structures of ERAP2 in complex with two phosphinic pseudotripeptide inhibitors. Both compounds are found in the catalytic site in a canonical orientation for transition-state analogues and util

SUBMITTER: Mpakali A 

PROVIDER: S-EPMC8842112 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature