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http://dx.doi.org/10.5483/BMBRep.2012.45.12.156

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

Son, Hyo Jeong (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
Ha, Seung Cheol (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
Hwang, Eun Young (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
Kim, Eun-A (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
Ahn, Jee-Yin (Departments of Molecular Cell Biology and Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine)
Choi, Soo Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
Publication Information
BMB Reports / v.45, no.12, 2012 , pp. 707-712 More about this Journal
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.
Keywords
Cysteine; Enzyme inhibition; Glutamate dehydrogenase; Isozymes; Palmitoyl-CoA;
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