UDP Glucuronosyltransferase:  Mechanism of a Detoxication   Enzyme
{'Code': '08070400', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Marcia Steinberg', 'PO_EMAI': None, 'PO_PHON': None}
An investigation into the mechanism of action of the                            membrane-bound detoxication enzyme UDP                                          glucuronosyltransferase is underway.  The specific aims of                      the study are to i) elucidate the kinetic mechanism of the                      enzyme using alternative substrates ii) probe the structure                     of the transition state of the enzymatic reaction using                         specifically designed alternative substrates and linear-free                    energy relationships iii) determine the effect of membrane or                   phospholipid environment on the transition state of the                         reaction by observing their effects on linear-free energy                       relationships iv) probe the topology of the active site of                      the enzyme toward sterically hindered chiral phenols.                           Alternative glucuronosyl-donating substrate having similar                      geometries but with leaving groups (e.g. UDP, UMPCH2P,                          UMPCHFP, and UMPCF2P) of different pKa will be synthesized                       and used to probe the amount and importance of bond-breaking                   in the transition-state.  Nucleophilicity of the aglycone                       will be varied by using the appropriately substituted phenol                    to examine the degree of bond-making in the transition state.                   The enzyme will be incorporated into different micellar or                      vesicular environments to determine the importance of                           membrane stereoselectivity of the enzyme and the equilibrium                    constant for glucuronidation of dihydrodiols is being                           determined in the reverse (deconjugation) reaction.  Finally,                   chiral phenols of known stereochemistry will be used to                         determine the extent to which the aglycone binding site can                     recognize chiral substrate surfaces.
{'FirstName': 'Richard', 'LastName': 'Armstrong', 'PI_MID_INIT': 'N', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Richard N Armstrong', 'EmailAddress': None, 'NSF_ID': '000298750', 'StartDate': '04/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'University of Maryland, College Park', 'CityName': 'COLLEGE PARK', 'ZipCode': '207425100', 'PhoneNumber': '3014056269', 'StreetAddress': '3112 LEE BUILDING', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Maryland', 'StateCode': 'MD', 'CONGRESSDISTRICT': '04', 'CONGRESS_DISTRICT_ORG': 'MD04', 'ORG_UEI_NUM': 'NPU8ULVAAS23', 'ORG_LGL_BUS_NAME': 'UNIVERSITY OF MARYLAND, COLLEGE PARK', 'ORG_PRNT_UEI_NUM': 'NPU8ULVAAS23'}
{'Name': None, 'CityName': None, 'StateCode': None, 'ZipCode': None, 'StreetAddress': None, 'CountryCode': None, 'CountryName': None, 'StateName': None, 'CountryFlag': None, 'CONGRESSDISTRICT': None, 'CONGRESS_DISTRICT_PERF': '""'}
{'Code': '1144', 'Text': 'Molecular Biophysics'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1987&All=true', 'xml': '8716307.xml'}