Document Detail

Identification of amino acid residues responsible for different GTP preferences of human glutamate dehydrogenase isozymes.
MedLine Citation:
PMID:  18261983     Owner:  NLM     Status:  MEDLINE    
Human glutamate dehydrogenase isozymes (hGDH1 and hGDH2) differ markedly in their inhibition by GTP. These regulatory preferences must arise from amino acid residues that are not common between hGDH isozymes. We have constructed chimeric enzymes by reciprocally switching the corresponding amino acid segments 390-465 in hGDH isozymes that are located within or near the C-terminal 48-residue antenna helix, which is thought to be part of the regulatory domain of mammalian GDHs. These resulted in triple mutations in amino acid sequences at 415, 443, and 456 sites that are not common between hGDH1 and hGDH2. The chimeric enzymes did not change their enzyme efficiency (k(cat)/K(m)) and expression level. Functional analyses, however, revealed that the chimeric mutants almost completely acquired the different GTP regulatory preference between hGDH isozymes. These results suggest that the 415, 443, and 456 residues acting in concert are responsible for the GTP inhibitory properties of hGDH isozymes.
Myung-Min Choi; Eun Young Hwang; Eun-A Kim; Jae-Wan Huh; Sung-Woo Cho
Related Documents :
19224193 - Isolation and characterisation of an lpa (low phytic acid) mutant in common bean (phase...
9417123 - Involvement of rabphilin3 in endocytosis through interaction with rabaptin5.
12227743 - S(n)1-like reactions of bicyclic alpha-amino ethers with sulfur, nitrogen, and carbon n...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-07
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  368     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-04     Completed Date:  2008-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  742-7     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, Republic of Korea.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amino Acid Sequence
Amino Acids / chemistry*
Binding Sites
Computer Simulation
Enzyme Activation
Glutamate Dehydrogenase / chemistry*
Guanosine Triphosphate / chemistry*
Isoenzymes / chemistry
Models, Chemical*
Molecular Sequence Data
Mutagenesis, Site-Directed
Protein Binding
Reg. No./Substance:
0/Amino Acids; 0/Isoenzymes; 86-01-1/Guanosine Triphosphate; EC Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Sequence determinants regulating fibrillation of human alpha-synuclein.
Next Document:  Discovery of the first SecA inhibitors using structure-based virtual screening.