STUDY OF SMALL UBIQUITININ LOKE MODIFIERS AND CHAPERONIC SIGNALING IN NON-INSULIN DEPENDENT DIABETES MELLITUS

Abstract

Small ubiquitin-related modifier (SUMO) family proteins function inpost-translational modifications of proteinsby covalently attaching to them. This helps in modification of many proteins involve in diverse cellular processes, like nuclear transport, transcriptional regulation, signal transduction andmaintenance of genome integrity. An enzyme pathway which is related to the ubiquitin pathway control theattachment between SUMO and proteins. Heat shock protein 27 (HSP27) helps stressed cells to survive in adverse conditions by accumulating in them. HSP27 function in the ubiquitination process is already known. Here, we showed that HSP27 is also involved in protein sumoylation, in the case of diabetes. It was found that HSP27 helps in increasing the number of cell proteins modified by small ubiquitin-like modifier (SUMO)-2/3. In stressed cells, HSP27 form large oligomer which binds to HSF1 and enters the nucleus which induces SUMO-2/3modification. Hence by this study we can say that HSP27 can be use as SUMO-E3 ligase specific for SUMO 2/3. Virtual screening of ligands and then docking against SUMO protein was performed using PatchDock and Swissdocksoftwares. ZINC53683754 [(2S)-8-{(tert-butoxycarbonyl) amino}-2-(1H-indole-3-oyl)octanoic acid] andZINC53683750 [(2S)-2-(1H-indole-3-yl)hexanoic acid] comes out to be good SUMO protein binders. This study proves that sumoylation has a role in the regulation of proteins involved in glucose metabolism. It identifies a new mechanism for the study of functions of SUMO proteins at the post-translational level and helps in identification of potential SUMO binding targets and potential ligand binders. It was found that drug docking significantly reduces the number of experiments and thereby cut cost while examining the utility of any chemical as a drug before going through any in vivo or in vitro analysis.