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Title: Enzyme kinetics and molecular modeling studies of G6PD<sub>Mahidol</sub> associated with acute hemolytic anemia
Authors: Lu, Hui-Ru
Tang, Qiong-Ling
Wang, Xin
Li, Hong-Jun
Yang, Yin-Feng
Li, Dan-Yi
Tong, Shu-Fen
Zhang, Chun-Hua
Zhu, Yue-Chun
Keywords: G6PD
Achang people
Acute hemolytic anemia
Enzyme kinetics
Crystal structure
Issue Date: Oct-2011
Publisher: NISCAIR-CSIR, India
Abstract: G6PD<sub>Mahidol</sub> enzyme is the most common variant in the Achang Chinese ethnic group and clinically manifests as class II. In this study, G6PD<sub>Mahidol</sub> enzyme was characterized by molecular modeling to understand its kinetics. G6PD<sub>Mahidol</sub>, G6PD<sup>G487A</sup> and G6PD<sup>WT</sup> proteins were heterologously expressed in the G6PD-deficient DF213<i style=""> E. coli</i> strain, purified and their steady-state kinetic parameters were determined. Compared with G6PD<sup>WT</sup>, the <i style="">K<sub>m</sub></i> and <i style="">V<sub>max</sub></i> of NADP<sup>+ </sup>with G6PD<sup>G487A </sup>were about 28-fold and 12-fold lower, respectively. The <i style="">K<sub>i</sub></i><sub> </sub>values of dehydroepiandrosterone (DHEA), NADPH and ATP with G6PD<sup>G487A</sup> showed 29.5-fold, 2.36-fold reduction and 1.83-fold increase, respectively. A molecular modeling of G6PD<sup>G487A </sup>was performed based on the X-ray structure of human G6PD (PDB: 2BH9). It is suggested that Ser-163 might affect the stability of G6PD<sup>G487A</sup> <img src='/image/spc_char/alpha.gif' border=0>-helix d and <img src='/image/spc_char/beta.gif' border=0>-strand E, besides the conformation of <img src='/image/spc_char/beta.gif' border=0>-strand D. In conclusion, the biochemical and structural properties of G6PD<sup>G487A </sup>and G6PD<sup>WT</sup> enzymes are significantly different, which may be responsible for clinical diversity of G6PD deficiencies.
Description: 316-324
ISSN: 0975-0959 (Online); 0301-1208 (Print)
Appears in Collections:IJBB Vol.48(5) [October 2011]

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