Molecular dynamics simulation studies of human DGAT1 and its substrates, acyl-CoA and diacylglycerol

Abstract

Diacylglycerol O-acyltransferase-1 (DGAT1) is an integral membrane protein that uses acyl-coenzyme A (acyl-CoA) and diacylglycerol (DAG) to catalyze the formation of triacylglycerides (TAG). At a final step of TAG biosynthesis process, the acyl transfer reaction occurs between the activated carboxylate group of the fatty acid and the free hydroxyl group on the glycerol backbone of DAG. How the two substrates access to their binding sites and interact with DGAT1 remains elusive. This study aims to determine the structural basis of DGAT1’s substrate recognition by investigating each substrate’s pathway to DGAT1’s catalytic reaction chamber.