UDP-galactopyranose mutase (UGM) is an enzyme that catalyzes the interconversion of UDP-galactopyranose (UDP-Galp) and UDP-galactofuranose (UDP-Galf). A combined NMR-computer modeling protocol was used to study wild type UGM and the W160A mutant UGM from Klebsiella pneumoniae complexed with substrates UDP-Galp and UDP-Galf , the natural inhibitor UDP, and the slowly-turned over substrate UDP-[3-F]-Galf. Computer models were generated by docking the ligands with AutoDock 3.0.5, followed by molecular dynamics using a modified GROMOS 53A6 force field. The CORCEMA-ST program, which uses a complete relaxation and exchange matrix to calculate saturation transfer difference NMR effects, yielded theoretical saturation transfer difference (STD) effects in the enzyme ligand complexes which were then compared to experimental STD effects. UDP-galactopyranose mutase was found to undergo an induced fit upon ligand binding. These rearrangements suggest that the modeled structures of the enzyme-substrate complexes may be more appropriate for the purposes of design of inhibitors of UGM.
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