Site-Specific Mutagenesis of Rat Oncomodulin
{'Code': '08070000', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Bruce L. Umminger', 'PO_EMAI': None, 'PO_PHON': None}
Oligonucleotide-directed mutagenesis will be used to                       study the structure and properties of the metal binding sites in                two, small, calcium-binding proteins that differ in their                       physiological functions.  The protein, oncomodulin, exhibits                    striking homology to the muscle protein, parvalbumin.                           Parvalbumin in muscle may be involved in buffering intracellular                calcium, but is devoid of the ability to trigger calcium-                       dependent interactions of contractile proteins.  Oncomodulin, on                the other hand, is capable of activating cyclic nucleotide                      phosphodiesterase in a manner reminiscent of calmodulin.  This                  functional difference between the two proteins is mirrored in                   their metal-binding properties.  Oncomodulin possesses one Ca/Mg                binding site and one Ca-specific site, while parvalbumin contains               two Ca/Mg sites.  The objectives of this project are:  1. To                    determine what factors differentiate a Ca-specific site (a                      "triggering" site) from a Ca/Mg site (a "relaxing" site), and 2.                to identify specific amino acid residues in oncomodulin that are                essential to the protein's regulatory capability.  An oncomodulin               expression plasmid has been constructed, and now single mutations               will be introduced into the oncomodulin coding sequence.  The                   effects of these mutations on the protein's metal-binding                       properties and regulatory ability will then be investigated.                    Luminescent lanthanide ion probes, together with conventional                   metal-binding assays, will be used to study the metal-binding                   properties of the altered proteins.  The ability of oncomodulin                 to stimulate heart cyclic nucleotide phosphodiesterase will be                  used as a probe of regulatory capability.                                            The family of intracellular calcium-binding proteins                       includes troponin C, calmodulin, parvalbumin, and vitamin D-                    dependent calcium-binding protein, in addition to oncomodulin.                  These proteins display a high degree of homology in their metal-                binding domains and are believed to have evolved from a common                  precursor.  There is, however, considerable variation in their                  metal binding properties.  Certain binding sites are quite                      specific for calcium and do not bind magnesium ion under                        physiological conditions, while other sites have affinity for                   both calcium and magnesium.  The metal-binding specificity is                   correlated with physiological function.  Calcium specific sites                 are involved in initiating ("triggering") biological processes,                 while Ca/Mg sites are not.  The molecular basis for the                         difference in function is not understood.  The proposed                         comparison of the detailed structure of oncomodulin, which has                  "triggering" activity, and parvalbumin, which does not, should                  provide important insight into this interesting and                             physiologically important question.
{'FirstName': 'Michael', 'LastName': 'Henzl', 'PI_MID_INIT': 'T', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Michael T Henzl', 'EmailAddress': 'henzlm@missouri.edu', 'NSF_ID': '000225483', 'StartDate': '06/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'New Mexico State University', 'CityName': 'LAS CRUCES', 'ZipCode': '88003', 'PhoneNumber': '5756461590', 'StreetAddress': '1050 STEWART ST.', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'New Mexico', 'StateCode': 'NM', 'CONGRESSDISTRICT': '02', 'CONGRESS_DISTRICT_ORG': 'NM02', 'ORG_UEI_NUM': 'J3M5GZAT8N85', 'ORG_LGL_BUS_NAME': 'NEW MEXICO STATE UNIVERSITY', 'ORG_PRNT_UEI_NUM': None}
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[{'Code': '111700', 'Text': 'CELLULAR PHYSIOLOGY'}, {'Code': '114100', 'Text': 'PHYSIOLOG & STRUCTURAL SYS'}]
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8801873.xml'}