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Computational approach to investigate the catalytic chemical reaction mechanism of glyoxysomal Malate Dehydrogenase
Author(s) -
Guterres Hugo,
Bell Ellis
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.463.6
Subject(s) - active site , hydride , transition state , malate dehydrogenase , chemistry , nad+ kinase , proton , catalysis , computational chemistry , physics , enzyme , biochemistry , organic chemistry , quantum mechanics , hydrogen
Geometry optimization calculation was used to find the minimum total energy and structure of the transition state during conversion of malate to oxaloacetate. During the reaction proton abstraction to H220 in the active site, and hydride transfer to NAD occur. Our primary goal was to develop a computational approach to examine the effects of active site and second sphere mutations in the activity of gMDH. Gaussian 03W was used to build the structure of the compounds, arrange their symmetry, and run the geometry optimization calculations. A truncated model including Histidine 220, malate and NAD was used to analyze the effect of the catalytic base. The result shows an imaginary frequency which indicates the presence of the transition state. The geometry structure of the transition state confirms the hydride transfer but the proton transfer is disoriented. This suggests that amino acids around the active site play important roles in facilitating the hydride and proton transfer. We have finished the transition state energy for the native gMDH and are working to find the total energy for transition state of mutants gMDH to facilitate the study of second sphere mutations. This work is supported by NSF Grant MCB 0448905 to EB.