Structure and Functional Study of Glutathione S-transferase cGSTM1-1 Complexed with Various Substrates
碩士 === 台北醫學院 === 細胞及分子生物研究所 === 88 === We elucidated the three-dimensional structure of mu-class glutathione S-transferase cGSTM1-1 co-crystallized with the glutathionyl conjugated 1,2-epoxy-3-(p-nitrophenoxy)propane (GS-EPNP) at 2.8A resolution. The product found in the active site was 1...
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| Format: | Others |
| Language: | zh-TW |
| Published: |
2000
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| Online Access: | http://ndltd.ncl.edu.tw/handle/33649622445030438421 |
| Summary: | 碩士 === 台北醫學院 === 細胞及分子生物研究所 === 88 === We elucidated the three-dimensional structure of mu-class glutathione S-transferase cGSTM1-1 co-crystallized with the glutathionyl conjugated 1,2-epoxy-3-(p-nitrophenoxy)propane (GS-EPNP) at 2.8A resolution. The product found in the active site was 1-hydroxy-2-(S-glutathionyl)-3- (p-nitrophenoxy) propane, instead of the conventionally decided 2-hydroxy isomer. The structure can explain the epoxidase activity of cGSTM1-1 to the substrates. The EPNP moiety orients towards Arg107(α4 helix), and Gln165(α6 helix ) in dimer AB and protrudes into a hydrophobic region formed by the loop connectingβ1 and α1 and part of the C-terminal tail in dimer CD. The phenoxyl ring forms strong ring stacking with the Trp209 side-chain in dimer CD. We hypothesize that these two conformations represent the EPNP moiety close to the initial and final stages of the reaction mechanism, respectively. And the conclusion was confirmed with the report of the mutagenesis and kinetic studies of cGSTM1-1.
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