title: Roles of cysteine residues in the inhibition of human glutamate dehydrogenase by palmitoyl-CoA.
abstract: Human glutamate dehydrogenase isozymes (hGDH1 and hGDH2) have been known to be inhibited by palmitoyl-CoA with a high affinity. In this study, we have performed the cassette mutagenesis at six different Cys residues (Cys59, Cys93, Cys119, Cys201, Cys274, and Cys323) to identify palmitoyl- CoA binding sites within hGDH2. Four cysteine residues at positions of C59, C93, C201, or C274 may be involved, at least in part, in the inhibition of hGDH2 by palmitoyl-CoA. There was a biphasic relationship, depending on the levels of palmitoyl-CoA, between the binding of palmitoyl-CoA and the loss of enzyme activity during the inactivation process. The inhibition of hGDH2 by palmitoyl-CoA was not affected by the allosteric inhibitor GTP. Multiple mutagenesis studies on the hGDH2 are in progress to identify the amino acid residues fully responsible for the inhibition by palmitoyl-CoA.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Son
authors.forename: Seung Cheol
authors.initials: SC
authors.lastname: Ha
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Hwang
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D019943:Amino Acid Substitution; D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry*; D005969:Glutamate Dehydrogenase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D010171:Palmitoyl Coenzyme A; D006160:Guanosine Triphosphate; D005969:Glutamate Dehydrogenase; D003545:Cysteine