Catalytic Site of Calmodulin-Dependent Protein Kinase
{'Code': '08070400', 'Directorate': {'LongName': 'Direct For Biological Sciences'}, 'Division': {'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Eve Ida Barak'}
Elucidating the molecular mechanisms by which                                   calcium/calmodulin activated enzymes aid transformation of                      regulatory calcium-signals into biochemical responses is the                    ultimate goal.  The proposal focuses on type II calmodulin-                     dependent protein kinase, a dodecameric enzyme of functionally                  identical subunits; each subunit is composed of catalytic,                      regulatory, and association domains.  As the location of the                    ATP-binding site has merely been inferred by sequence                           comparison with related protein kinases, and the corresponding                  site for protein substrates is unknown, these continuing                        investigations are directed towards characterizing both of                      these substrate-binding sites.  Because ligand-promoted                         instability and aggregation have hampered studies with the                      holoenzyme, a catalytic fragment will be used.  This monomeric                  domain has the added advantage of needing neither calmodulin                    nor autophosphorylation to be fully active.  This domain will                   be characterized and used to probe the kinetic reaction                         mechanism, to study substrate-binding, and to identify amino                    acid side chains which are lining the two substrate-binding                     pockets.  The location of the ATP-binding site on the protein                   sequence of the kinase will be verified by affinity and                         photoaffinity labeling with analogs of ATP.  Photoaffinity                      labeling with photoreactive peptide substrates will be used to                                                                                                  locate the second site.  Calcium is one of the most important                                                                                                   intracellular regulators and second messengers of biological                                                                                                    systems.  The intracellular levels of Ca2+ are increased upon                                                                                                   stimulation by a variety of extracellular agents, such as                                                                                                       hormones, drugs, and neurotransmitters.  The increase in the                                                                                                    concentration of Ca2+ triggers a serious of regulatory events                                                                                                   that ultimately alter many processes, including those                                                                                                           responsible for muscle contraction and the transmission of                                                                                                      nerve impulses.  Activation of calmodulin-dependent protein                                                                                                     kinase and calcinerin seem to be part of the mechanism by which                                                                                                 the Ca2+ calmodulin complex initiates biochemical responses at                                                                                                  the synapse because a detailed understanding of the structure,                                                                                                  function and regulation of these enzymes may aid in elucidating                                                                                                 the molecular events at the synapse, studies of these                                                                                                           interconverting enzymes are of considerable interest.
{'FirstName': 'Marita', 'LastName': 'King', 'EmailAddress': 'mmking@magnus.acs.ohiostate.edu', 'StartDate': '02/01/1989', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Ohio State University Research Foundation -DO NOT USE', 'CityName': 'Columbus', 'ZipCode': '432101016', 'PhoneNumber': '6146888734', 'StreetAddress': '1960 KENNY RD', 'CountryName': 'United States', 'StateName': 'Ohio', 'StateCode': 'OH'}
[{'Code': '1144', 'Text': 'Molecular Biophysics'}, {'Code': '9120', 'Text': 'CROSS-DIRECTORATE PROGRAMS'}]
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8816258.xml'}