| Research work of this thesis is composed of the following two parts:1. Fatty acid binding protein 4(FABP4), a member of the fatty acid binding protein family, locates in the adipocytes and macrophages. As fatty acid chaperone, it plays center roles in lipid transport, lipolysis and liposynthesis, and has been proved to be involved in the lipid signaling and inflammatory responses. Inhibitors of FABP4 are promising treatments for the diabetes and atherosclerosis. In the first part of my thesis, the complex structures of FABP4 with aspirin and its derivative are determined. It has been proposed that aspirin can be used for atherosclerosis treatement via FABP4 inhibiting pathway. Compared to the electrostatic interaction provided by the hydrophilic residues, the structural information further demonstrates that C-H-π "edge-to-face" interaction between the phenyl CH group of hydrophobic residue Phe16 and the aromatic ring of aspirin takes priority over stablizing the ligands binding. This result might provide a better insight into designing new inhibitors of FABP4 with high selectivity.2. Human polyadenosine-binding protein nuclear 1 (PABPN1) binds to poly (A) tail in the nucleus and involves in the regulation of the mRNA post-transcription. PABPN1 has a single RNA recognition motif (RRM), and biochemical evidences and its homologous studies have suggested that RRM might exist as a dimer in vivo. To date, the polymerization of the PABPN1 in the physiological status and the mechanism of its binding to RNA have not been determined. In my gel-filtration chromatography and SDS-PAGE experiments, it is proved that CC-RRM domain of PAPBN1 exists as a dimer in the solution. To further investigate the mode of dimerization, small angle X-ray scattering is applied to obtain robust structural conformation of the PABPN1 in the solution. According to the SAXS information provided and homologous alignment results, a probable dimerization form has been proposed... |
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