Maltase Glucoamylase (MGAM): Putting Diabetes in its Place! (LB85)

Abstract

By 2050 1 in 3 Americans will have type 2 diabetes, a disease characterized by excessively high blood glucose levels. Typically, diabetes is treated with regular insulin injections and blood sugar monitoring. For centuries, Aryuvedic medicine has had a massive following, in part due to its natural remedies for diabetes deriving from an Indian herb, Salacia reticulata. These extracts were found to contain α‐glucosidase inhibitors, a class of anti‐diabetic drugs that competitively inhibit intestinal starch‐digesting enzymes such as human Maltase Glucoamylase (MGAM). As MGAM is responsible for catalyzing the final glucose‐releasing step of starch digestion, inhibiting MGAM would delay glucose absorption into the bloodstream. The Ashbury SMART (Students Modeling a Research Topic) Team modeled MGAM in complex with two inhibitors, salacinol and Acarbose, (PDBID 2QMJ & 3L4Z) using Jmol and 3D printing technology. The binding of ‐glucosidase inhibitor salacinol, derived from Salacia reticulata extracts and Acarbose, a currently prescribed α‐glucosidase inhibitor will be compared in the MGAM active site. Notably, both inhibitors interact with MGAM residues Asp327 and His600 through ring hydroxyl groups, however salacinol contributes additional electrostatic interaction between its sulfonium center and the catalytic nucleophile Asp443.Grant Funding Source: Supported by grants from the NIH‐SEPA and NIH‐CTSA.