Key features of inhibitor binding to the human mitochondrial pyruvate carrier hetero-dimer.

ABSTRACT:

Objective

The mitochondrial pyruvate carrier (MPC) has emerged as a promising drug target for metabolic disorders, including non-alcoholic steatohepatitis and diabetes, metabolically dependent cancers and neurodegenerative diseases. A range of structurally diverse small molecule inhibitors have been proposed, but the nature of their interaction with MPC is not understood, and the composition of the functional human MPC is still debated. The goal of this study was to characterise the human MPC protein in vitro, to understand the chemical features that determine binding of structurally diverse inhibitors and to develop novel higher affinity ones.

Methods

We recombinantly expressed and purified human MPC hetero-complexes and studied their composition, transport and inhibitor bi

SUBMITTER: Tavoulari S 

PROVIDER: S-EPMC8968063 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature