an enzymatic atavist revealed in dual pathways for water activation一个酶显隔代遗传物在对水的双重途径激活.pdfVIP

PLoS BIOLOGY An Enzymatic Atavist Revealed in Dual Pathways for Water Activation 1 2 1 3 2 3 Donghong Min , Helen R. Josephine , Hongzhi Li , Clemens Lakner , Iain S. MacPherson , Gavin J. P. Naylor , David Swofford3, Lizbeth Hedstrom2,4*, Wei Yang1,5,6,7* 1 School of Computational Science, Florida State University, Tallahassee, Florida, United States of America, 2 Department of Biochemistry, Brandeis University, Waltham, Massachusetts, United States of America, 3 Department of Biological Sciences, Florida State University, Tallahassee, Florida, United States of America, 4 Department of Chemistry, Brandeis University, Waltham, Massachusetts, United States of America, 5 Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America, 6 Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, United States of America, 7 College of Life Science, Nankai University, Tianjin 300071, China Inosine monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the biosynthesis of guanine nucleotides. This reaction involves two different chemical transformations, an NAD-linked redox reaction and a hydrolase reaction, that utilize mutually exclusive protein conformations with distinct catalytic residues. How did Nature construct such a complicated catalyst? Here we employ a ‘‘Wang-Landau’’ metadynamics algorithm in hybrid quantum mechanical/molecular mechanical (QM/MM) simulations to investigate the mechanism of the hydrolase react