Specificity of Ubiquitin-Dependent Proteases
{'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}
The long term goal of this research is to define the                            specificity, mechanism and physiological significance of the                    ubiquitin-dependent protein degradation system of eucaryotic                    cells.  This soluble multi-enzyme system has been best                          characterized from reticulocytes where it appears to play a                     role in the degradation of abnormal proteins and                                intracellular organelles during maturation.                                     The objective of this proposal is to provide a basic                            biochemical description of the protease(s) of the system and                    the metabolism of conjugated proteins by these                                  proteases.                                                                                                                                                      Ubiquitin is conjugated to a large number of proteins in the                    cell by the formation of an isoamide bond between the                           carboxyl-terminus of ubiquitin and the amino groups of the                      target proteins.  It is these conjugates which are thought to                   be substrates for the proteases of the system.  Understanding                   of the proteolytic mechanisms has been hampered by the lack                     of pure, defined substrates.  This has slowed the development                   of assays and,  therefore, the purification of the proteases.                   The proposed work will address this problem by synthesizing                     and characterizing a number of these conjugates using the                       carboxyl-terminal acyl azide of ubiquitin.  These substrates                    will be used to purify and characterize the components of the                   proteases, as well as to determine the specificity and                          architecture of the multi-enzyme complex which catalyzes                        these reactions.  Additionally, the nature of the ATP                           requirement for proteolytic action will be examined.  The                       knowledge gained from these studies should form the basis for                   the design of specific inhibitors of this system, as well as                    for the cloning and genetic manipulation of the component                       peptides of the system.
{'FirstName': 'Keith', 'LastName': 'Wilkinson', 'PI_MID_INIT': 'D', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Keith D Wilkinson', 'EmailAddress': 'genekdw@bimcore.emory.edu', 'NSF_ID': '000323011', 'StartDate': '09/01/1987', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Emory University', 'CityName': 'ATLANTA', 'ZipCode': '303221061', 'PhoneNumber': '4047272503', 'StreetAddress': '201 DOWMAN DR NE', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Georgia', 'StateCode': 'GA', 'CONGRESSDISTRICT': '05', 'CONGRESS_DISTRICT_ORG': 'GA05', 'ORG_UEI_NUM': 'S352L5PJLMP8', 'ORG_LGL_BUS_NAME': 'EMORY UNIVERSITY', 'ORG_PRNT_UEI_NUM': None}
{'Name': 'Emory University School of Medicine', 'CityName': 'Atlanta', 'StateCode': 'GA', 'ZipCode': '30322', 'StreetAddress': None, 'CountryCode': 'US', 'CountryName': 'United States', 'StateName': 'Georgia', 'CountryFlag': '1', 'CONGRESSDISTRICT': '05', 'CONGRESS_DISTRICT_PERF': 'GA05'}
{'Code': '1144', 'Text': 'Molecular Biophysics'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1987&All=true', 'xml': '8703828.xml'}