Physical Sciences and Mathematics Commons^™

Substrate Induced Structural And Dynamics Changes In Human Phosphomevalonate Iinase And Implications For Mechanism, Andrew Lawrence Olson, Huili Yao, Timothy J. Herdendorf, Henry M. Miziorko, Supa Hannongbua, Patchareenat Saparpakom, Sheng Cai, Daniel S. Sem

Chemistry Faculty Research and Publications

Phosphomevalonate kinase (PMK) catalyzes an essential step in the mevalonate pathway, which is the only pathway for synthesis of isoprenoids and steroids in humans. PMK catalyzes transfer of the γ-phosphate of ATP to mevalonate 5-phosphate (M5P) to form mevalonate 5-diphosphate. Bringing these phosphate groups in proximity to react is especially challenging, given the high negative charge density on the four phosphate groups in the active site. As such, conformational and dynamics changes needed to form the Michaelis complex are of mechanistic interest. Herein, we report the characterization of substrate induced changes (Mg-ADP, M5P, and the ternary complex) in PMK using …