INVESTIGATING THE ROLE OF PROLINE KINK IN P50RHOGAP AND THE CHARACTERIZATION OF BNIP-H BINDING PARTNER KGA AND COMPLEXES

Abstract

The BCL2 and Nineteen kDa Interacting Protein (BNIP) functions as a key player in protein interactions. The BNIP family constitutes the characteristic BNIP-2 and Cdc42GAP Homology or BCH domain that behaves as a versatile scaffold protein. In this thesis, we report the first representative structure of the BCH domain from the S. pombe homologue of human p50RhoGAP (yBCH), a key mediator of active RhoA. The p50RhoGAP is involved in pathways concerning cell morphology and apoptosis. Here, investigations regarding dimerization, RhoA binding, Proline kink and phosphorylation are done. Additionally, in this thesis the near full-length crystal structure of Kidney-Type Glutaminase (KGA) was determined. A novel allosteric site with a conserved inhibition mechanism was reported. Finally, the thesis reports some crucial characteristics of BNIP-H (BNIP-2 homology), an important neurological protein. BNIP-H is involved in kinesin binding, cholinergic complex formation and ubiquitination. This work will help understand the molecular mechanism of many diseases.