Exploring the Mechanism of Binding of UDP-Galactopyranose to UDP-Galactopyranose Mutase by STD-NMR Spectroscopy and Molecular Modeling

• DOI: 10.1021/bi0513406
• Publication Date: 2005-10-25T04:23:01Z
• Authors: Yue Yuan; Xin Wen; David A. R. Sanders; B. Mario Pinto
• Keywords: Mutase; Affinities; Cooperative binding; Docking (animal)

UDP-galactopyranose mutase (UGM) is the key enzyme involved in biosynthesis of Galf. In this study, reliable structural binding modes natural substrate, UDP-Galp, and inhibitor, UDP, UGM active site were provided with combined use STD-NMR spectroscopy, molecular modeling, CORCEMA-ST calculations. UDP-Galp UDP exhibited similar epitopes recognized by UGM. However, relative affinities ligands changed dramatically upon reduction UGM, as explored competitive experiments. competes for to especially when its reduced state. Docking studies predicting mode within two monomers possibility that mobile loop might act a gateway substrate binding, structure cleft monomer A be closer approximation substrate-bound than B. Important information regarding critical interactions has been obtained.