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|Title:||Enzyme kinetics and molecular modeling studies of G6PD<sub>Mahidol</sub> associated with acute hemolytic anemia|
Acute hemolytic anemia
|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.|
|ISSN:||0975-0959 (Online); 0301-1208 (Print)|
|Appears in Collections:||IJBB Vol.48(5) [October 2011]|
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