Enzyme kinetics and molecular modeling studies of G6PD<sub>Mahidol</sub> associated with acute hemolytic anemia
IR@NISCAIR: CSIR-NISCAIR, New Delhi - ONLINE PERIODICALS REPOSITORY (NOPR)
View Archive Info| Field | Value | |
| Creator |
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 |
|
| Date |
2011-10-21T11:01:25Z
2011-10-21T11:01:25Z 2011-10 |
|
| Identifier |
0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/12939 |
|
| Description |
316-324
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. |
|
| Language |
en_US
|
|
| Publisher |
NISCAIR-CSIR, India
|
|
| Rights |
<img src='http://nopr.niscair.res.in/image/cc-license-sml.png'> <a href='http://creativecommons.org/licenses/by-nc-nd/2.5/in' target='_blank'>CC Attribution-Noncommercial-No Derivative Works 2.5 India</a>
|
|
| Source |
IJBB Vol.48(5) [October 2011]
|
|
| Subject |
G6PD
Achang people Acute hemolytic anemia Enzyme kinetics Crystal structure |
|
| Title |
Enzyme kinetics and molecular modeling studies of G6PD<sub>Mahidol</sub> associated with acute hemolytic anemia
|
|
| Type |
Article
|
|