CHEMICAL MECHANISM OF HOMOCITRATE SYNTHASE FROM Saccharomyces cerevisiae

ISBN-13: 9783639161557 / Angielski / Miękka / 2009 / 164 str.

Jinghua Qian

Opis

Homocitrate synthase (HCS1) (acetyl-coenzyme A:2-ketoglutarate C-transferase; E.C. 2.3.3.14)catalyzes the first and regulated step in thea-aminoadipate pathway for lysine synthesis. The pH dependence of the kinetic parameters, isotopeeffects, and dissociation constants for competitiveinhibitors are used to probe the chemical mechanismof HCS. A general acid-base chemical mechanism isproposed. site-directed mutagenesis was used tochange the three active site residues of HCS, and theresulting mutant enzymes were characterized usinginitial velocity studies, the pH dependence of thekinetic parameters and isotope effects. Datacombined with a constant pH molecular dynamicssimulation study suggest a catalytic dyad, comprisedof Glu-155 and His-309, functions as a general baseto deprotonate the methyl group of AcCoA.

O autorze

Jinghua Qian had his Ph.D. degree in May,2008 from University of
Oklahoma. During that time, he worked with Dr. Paul F. Cook on
the chemical mechanism of homocitrate synthase from S.
cerevisiae. He was born in Liyang, Jiangsu, P.R. China. He
married to Jing Wen and has a son, James Z. Qian.