Mechanism of the B6 Enzyme O-Acetylserine Sulfhydrylase
{'Code': '08070400', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Eve Ida Barak', 'PO_EMAI': None, 'PO_PHON': None}
This work will be carried out to further our understanding of                   the mechanism of O-acetylserine sulfhydrylase specifically and                   -replacement reactions catalyzed by PLP enzymes in general.                    Two specific aims:  First, the acid-base chemistry catalyzed by                 enzyme will be elucidated.  This aspect will make use of                        initial velocity studies to measure various values for                          inhibitors competitive with the substrates as a function of pH.                 In addition, spectral intermediates along the reaction pathway                  with a finite lifetime will be titrated to determine whether                    enzyme and/or cofactor pK values are perturbed as the reaction                  proceeds.  Second, the location and amount of limitation of                     rate determining steps will be determined.  These studies will                  make use of primary and secondary deuterium, solvent deuterium                  and multiple isotope effects and their pH dependence.  The                      isotope effect data should allow pinpointing the location of                    rate determining steps and permit a mechanistic framework for                   interpretation of covalent catalysis.  Finally, positional                      isotope exchange in which the ester carbonyl oxygen is labeled                  with 180 will be used to determine whether product release in                   the first half-reaction is partially or completely rate                         limiting.                                                                                                                                                       The broad range of experiments proposed here is likely to give                  considerably more detailed insight into the mode of action of                   this important enzyme then is available today, and the prospect                 that this information may later on be used in some intriguing                   studies on the catalytic consequences of protein-protein                        interaction gives the project an additional dimension.   Dr.                    Cook is well qualified to carry out this work.
{'FirstName': 'Paul', 'LastName': 'Cook', 'PI_MID_INIT': 'F', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Paul F Cook', 'EmailAddress': 'pcook@ou.edu', 'NSF_ID': '000093951', 'StartDate': '02/15/1989', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'University of North Texas', 'CityName': 'DENTON', 'ZipCode': '762051132', 'PhoneNumber': '9405653940', 'StreetAddress': '1112 DALLAS DR STE 4000', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Texas', 'StateCode': 'TX', 'CONGRESSDISTRICT': '13', 'CONGRESS_DISTRICT_ORG': 'TX13', 'ORG_UEI_NUM': 'G47WN1XZNWX9', 'ORG_LGL_BUS_NAME': 'UNIVERSITY OF NORTH TEXAS', 'ORG_PRNT_UEI_NUM': None}
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{'Code': '114400', 'Text': 'Molecular Biophysics'}
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