Life Sciences & Biotechnology
Title : | Deciphering the sequence and structural signatures of the product specificity of Protein Arginine Methyltransferases in health and disease |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Structural Biology, Epigenetics |
Principal Investigator : | Dr. Sreenivas Chavali, Indian Institute of Science Education and Research (IISER), Tirupati, Andhra Pradesh |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | schavali@iisertirupati.ac.in |
Details
Executive Summary : | Arginine methylation is a crucial post-translation modification in proteins, affecting various biological processes. Protein Arginine methyltransferases (PRMTs) are classified into three types based on the type of methylation: Type I, Type II, and Type III. Dysregulation of these enzymes is linked to various human diseases, such as cancers. The PRMT family contains a conserved catalytic domain that catalyzes methyl transfer activity. All types of PRMTs generate monomethylarginine (MMA), with type I enzymes catalyzing the subsequent generation of asymmetric dimethylarginine (ADMA), type II enzymes catalyzing the production of symmetric dimethylarginine (SDMA), and type III enzymes catalyzing the formation of ω-NG-monomethylarginine (MMA). However, a comprehensive understanding of molecular signatures and specificity for distinct catalytic activities across the three types of PRMTs is still lacking. This research aims to elucidate the design principles underlying core and specific PRMT functionality based on the nature of the product generated. The study will use extensive sequence and structural analysis of 1822 proteins to identify core and type-specific signatures of PRMTs, map cancer mutations at these functional sites, and perform MD simulations to study their impact. The research aims to unravel the important sequence and structural determinants of PRMT-specific activity, providing the impetus to develop targeted inhibitors. The knowledge and deliverables from this research will shed light on a different facet of physiology and pathophysiology of PRMTs, paving the path for identifying new drug targets, developing inhibitors, and safer therapeutics. |
Total Budget (INR): | 63,11,036 |
Organizations involved