Roles of cysteine residues in the inhibition of human glutamate dehydrogenase by palmitoyl-CoA
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 sit...
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| Format: | Article |
| Language: | English |
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Korean Society for Biochemistry and Molecular Biology
2012-12-01
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| Series: | BMB Reports |
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| Online Access: | http://www.jbmb.or.kr/jbmb/pdf.php?data=MTMwMTE0MTVAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0NS0xMiU1RDEyMTIyNjE2MjRfJTI4NzA3LTcxMiUyOUJNQl8xMi0xNTYucGRm |
| Summary: | 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. |
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| ISSN: | 1976-6696 1976-670X |