Reinemer P, Dirr H W, Ladenstein R, Huber R, Lo Bello M, Federici G, Parker M W
Max-Planck-Institut für Biochemie, Martinsried, Germany.
J Mol Biol. 1992 Sep 5;227(1):214-26. doi: 10.1016/0022-2836(92)90692-d.
The three-dimensional structure of human class pi glutathione S-transferase from placenta (hGSTP1-1), a homodimeric enzyme, has been solved by Patterson search methods and refined at 2.8 A resolution to a final crystallographic R-factor of 19.6% (8.0 to 2.8 A resolution). Subunit folding topology, subunit overall structure and subunit association closely resembles the structure of porcine class pi glutathione S-transferase. The binding site of a competitive inhibitor, S-hexylglutathione, is analyzed and the locations of the binding regions for glutathione (G-site) and electrophilic substrates (H-site) are determined. The specific interactions between protein and the inhibitor's glutathione peptide are the same as those observed between glutathione sulfonate and the porcine isozyme. The H-site is located adjacent to the G-site, with the hexyl moiety lying above a segment (residues 8 to 10) connecting strand beta 1 and helix alpha A where it is in hydrophobic contact with Tyr7, Phe8, Val10, Val35 and Tyr106. Catalytic models are discussed on the basis of the molecular structure.
人胎盘来源的π类谷胱甘肽S-转移酶（hGSTP1-1）是一种同二聚体酶，其三维结构已通过帕特森搜索法解析，并在2.8 Å分辨率下进行了精修，最终晶体学R因子为19.6%（分辨率范围8.0至2.8 Å）。亚基折叠拓扑结构、亚基整体结构和亚基缔合与猪π类谷胱甘肽S-转移酶的结构极为相似。对竞争性抑制剂S-己基谷胱甘肽的结合位点进行了分析，并确定了谷胱甘肽（G位点）和亲电底物（H位点）的结合区域位置。蛋白质与抑制剂的谷胱甘肽肽之间的特异性相互作用与谷胱甘磺酸酯和猪同工酶之间观察到的相互作用相同。H位点位于G位点附近，己基部分位于连接β1链和αA螺旋的片段（残基8至10）上方，在该位置它与Tyr7、Phe8、Val10、Val35和Tyr106形成疏水接触。基于分子结构对催化模型进行了讨论。
