Structural analysis of the redox regulation of human Branched Chain Aminotransferase

Speaker: Dr. Ming Dong, from the Department of Chemistry, NC A&T State University

When: 11am, 2/14/2020

Abstract:

The hBCAT catalyzes the transamination of the branched chain amino acids, leucine, valine, isoleucine, and α-ketoglutarate to their respective α-keto acids and glutamate. hBCAT activity is regulated by a CXXC center located approximately 10 Å from the active site. This redox active center facilitates recycling between its reduced and oxidized state representing hBCAT in its active and inactive form, respectively. Site directed mutagenesis of the redox sensor (C315) results in a significant loss of activity, with no loss reported for mutation of the resolving cysteine (C318). Crystal structure of the oxidized form of C318A variant was used to better understand the contribution of the individual cysteines and their oxidation state. The structure reveals the modified CXXC center in a conformation similar to the oxidized wild type, supporting the notion that its regulatory mechanism depends on switching the C315 side chain between active and inactive conformations. Moreover, the structure reveals conformational differences in the N-terminal and inter-domain region that may correlate with the inactivated state of the CXXC center.