Structure and Dynamics of Meprin β in Complex with a Hydroxamate-Based Inhibitor.

ABSTRACT: The astacin protease Meprin β represents an emerging target for drug development due to its potential involvement in disorders such as acute and chronic kidney injury and fibrosis. Here, we elaborate on the structural basis of inhibition by a specific Meprin β inhibitor. Our analysis of the crystal structure suggests different binding modes of the inhibitor to the active site. This flexibility is caused, at least in part, by movement of the C-terminal region of the protease domain (CTD). The CTD movement narrows the active site cleft upon inhibitor binding. Compared with other astacin proteases, among these the highly homologous isoenzyme Meprin α, differences in the subsites account for the unique selectivity of the inhibitor. Although the inhibitor shows substantial flexibility in orient

SUBMITTER: Linnert M 

PROVIDER: S-EPMC8197800 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature