Predicting substrate selectivity between UGT1A9 and UGT1A10 using molecular modelling and molecular dynamics approach

摘要: Uridine 5′-diphospho-glucuronosyltransferase-1A9 (UGT1A9) expressed in the liver, shows good sequence identity with UGT1A10, intestine. Both uridine 5′-diphospho-glucuronosyltransferase (UGT) isoforms show comprehensive overlapping substrate selectivity but there are differences stereoselectivity, regiospecificity and rate of glucuronidation substrates. Multiple alignment analyses UGT1A9 UGT1A10 showed that 13% residues N-terminal domain (NTD) non-identical between them. Herein, authors attempted homology modelling validation using software tools reported mutagenic studies. A molecular docking study known substrates is performed on models. The ranging from 111 to 117 were identified play a central role selectivity. However, binding by Ser111, Gly115 Leu117 Gly111, Asp11...