Structural Analysis of the Redox Regulated Human Branched Chain Aminotransferase

The human branched chain aminotransferase proteins (hBCAT), hBCATm (mitochondrial) and hBCATc (cytosolic), catalyze the transamination of the branched chain amino acids (BCAA), leucine, valine and isoleucine, to their respective α-keto acids and glutamate. Subsequent oxidation of the resulting α-keto acids, by the branched chain α-keto acid dehydrogenase complex (BCKDC), generates acyl-CoA, which enters the TCA cycle. Mitochondrial BCAT (hBCATm) is found in the pancreas, kidney, stomach and brain, is thought to be responsible for the majority of transamination outside the central nervous system. Meanwhile, the cytosolic isoform (hBCATc) is predominantly expressed in the brain and the peripheral nervous system, as well as the placenta and ovary. These enzymes play significant roles in amino acid metabolism and whole-body nitrogen shuttling, in particular with respect to the de novo synthesis of the neurotransmitter glutamate in the brain. Interestingly, the transamination is regulated by the redox center CXXC motif of the protein, where the mutants of the redox center leads to a compromised hBCAT activity. Our goal is to have a deeper understanding of the redox regulation of hBCAT with structural analysis