MOLECULAR-STRUCTURE AT 1-CENTER-DOT-8-ANGSTROM OF MOUSE-LIVER CLASS-PI GLUTATHIONE-S-TRANSFERASE COMPLEXED WITH S-(P-NITROBENZYL)GLUTATHIONE AND OTHER INHIBITORS
MOLECULAR-STRUCTURE AT 1-CENTER-DOT-8-ANGSTROM OF MOUSE-LIVER CLASS-PI GLUTATHIONE-S-TRANSFERASE COMPLEXED WITH S-(P-NITROBENZYL)GLUTATHIONE AND OTHER INHIBITORS
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DOI：
10.1006/jmbi.1994.1232
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发表时间：
1994-04-01
影响因子：
5.6
通讯作者：
COLL, M
中科院分区：
文献类型：
--
作者：
GARCIASAEZ, I;PARRAGA, A;COLL, M
本文用X射线衍射法测定了小鼠肝中π型谷胱甘肽S-转移酶YfYf与邻硝基苯甲基谷胱甘肽复合物的三维晶体结构。此外，还测定了谷胱甘肽磺酸和S-己基谷胱甘肽的两种配合物，其分离度分别为1.9和2.2 μ m。高分辨率的S-（对硝基苄基）谷胱甘肽复合物允许详细分析的活性位点，包括疏水（H-）亚位点。硝基苄基部分占据疏水口袋，其芳环夹在Phe 8和Tyr 108的羟基之间。两个残基Gly 41和Leu 42的插入;相对于猪酶，将螺旋αB分成α螺旋和310螺旋。α-螺旋C端的羰基氧原子和310螺旋N端的酰胺NH基团之间的水桥提供了这两个二级元件之间的结构连续性。Tyr 7似乎是唯一接近谷胱甘肽硫原子的残基，而三个保守的水分子位于所有复合物的周围区域。在结构分析的基础上，对酶的作用机理进行了探讨.
The three-dimensional crystal structure of π class glutathione S-transferase YfYf from mouse liver complexed with the inhibitorS-(p-nitrobenzyl)glutathione has been determined at 1·8 Å resolution by X-ray diffraction. In addition two complexes with glutathione sulphonic acid andS-hexylglutathione have been determined at resolutions of 1·9 and 2·2 Å, respectively. The high resolution of theS-(p-nitrobenzyl)glutathione complex allows a detailed analysis of the active site including the hydrophobic (H-) subsite. The nitrobenzyl moiety occupies a hydrophobic pocket with its aromatic ring sandwiched between Phe8 and the hydroxyl group of Tyr108. An insertion of two residues Gly41 and Leu42; with respect to the pig enzyme, splits helix αB into an α-helix and a 310helix. Water bridges between carbonyl oxygen atoms of the α-helix at its C terminus and the amide NH groups of the 310helix at its N terminus provide structural continuity between these two secondary elements. Tyr7 appears to be the only residue close to the sulphur atom of glutathione, while three conserved water molecules lie in the surrounding area in all complexes. The enzyme mechanism is discussed on the basis of the structural analysis.