Roles of cysteine residues in the inhibition of human glutamate dehydrogenase by palmitoyl-CoA

• Main Author: Sung-Woo Cho
• Format: Article
• Language: English
• Published: Korean Society for Biochemistry and Molecular Biology 2012-12-01
• Series: BMB Reports
• Subjects: Cysteine; Enzyme inhibition; Glutamate dehydrogenase; Isozymes; Palmitoyl-CoA
• Online Access: http://www.jbmb.or.kr/jbmb/pdf.php?data=MTMwMTE0MTVAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0NS0xMiU1RDEyMTIyNjE2MjRfJTI4NzA3LTcxMiUyOUJNQl8xMi0xNTYucGRm

Human glutamate dehydrogenase isozymes (hGDH1 andhGDH2) have been known to be inhibited by palmitoyl-CoAwith a high affinity. In this study, we have performed the cassettemutagenesis at six different Cys residues (Cys59, Cys93,Cys119, Cys201, Cys274, and Cys323) to identify palmitoyl-CoA binding sites within hGDH2. Four cysteine residuesat positions of C59, C93, C201, or C274 may be involved, atleast in part, in the inhibition of hGDH2 by palmitoyl-CoA.There was a biphasic relationship, depending on the levels ofpalmitoyl-CoA, between the binding of palmitoyl-CoA and theloss of enzyme activity during the inactivation process. The inhibitionof hGDH2 by palmitoyl-CoA was not affected by theallosteric inhibitor GTP. Multiple mutagenesis studies on thehGDH2 are in progress to identify the amino acid residuesfully responsible for the inhibition by palmitoyl-CoA.