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Effects of Nucleotides on Changes in Flexibility & Allosteric Interactions in Glutamate Dehydrogenase
Author(s) -
Scheel Carolyn,
Bell Ellis
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.503.5
Subject(s) - allosteric regulation , isothermal titration calorimetry , chemistry , glutamate dehydrogenase , ligand (biochemistry) , gtp' , allosteric enzyme , nucleotide , protein subunit , cofactor , biophysics , nad+ kinase , stereochemistry , biochemistry , glutamate receptor , enzyme , biology , receptor , gene
Higher eukaryotic glutamate dehydrogenases exhibit complex homo and hetero tropic regulation involving subunit interactions and ligand induced conformational changes. Previous have shown that the amino acid substrates, glutamate or norvaline have differential effects on local and global stability of the protein. To investigate the effects of nucleotide cofactors [NAD(H) and NADP(H)] and the allosteric regulators ADP and GTP similar approaches, using Limited proteolysis, Differential Scanning Calorimetry, Dynamic Light Scattering have been used in combination with Isothermal Titration Calorimetry to study ligand induced changes in local flexibility and stability. Overall these studies indicate that both activity and allosteric regulation of this complex enzyme are linked to changes in conformational flexibility rather than discrete ligand induced changes in conformation. This research is supported by a Grant from the National Science Foundation: MCB 0448905 to EB