Modeling the Role of a Flexible Loop and Active Site Side Chains in Hydride Transfer Catalyzed by Glycerol-3-phosphate Dehydrogenase
Anil Ranu Mhashal, Adrian Romero‐Rivera, Lisa S. Mydy, Judith R. Cristobal, Andrew M. Gulick, John P. Richard, Shina Caroline Lynn Kamerlin
Abstract
, upon truncating this residue, as loop closure is essential for both correct positioning of key catalytic residues in the active site, as well as sequestering the active site from the solvent. Taken together, our data highlight the importance of this ligand-gated conformational change in catalysis, a feature that can be exploited both for protein engineering and for the design of allosteric inhibitors targeting this biomedically important enzyme.
Topics & Concepts
ChemistryActive siteStereochemistryCatalytic cycleConformational changeSide chainEnzyme kineticsEnzyme catalysisCatalysisBiochemistryOrganic chemistryPolymerEndoplasmic Reticulum Stress and DiseaseProtein Structure and DynamicsEnzyme Structure and Function