Cardoso Rosa M F, Daniels Douglas S, Bruns Christopher M, Tainer John A
Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Proteins. 2003 Apr 1;51(1):137-46. doi: 10.1002/prot.10345.
The 26-kDa glutathione S-transferase from Schistosoma japonicum (Sj26GST), a helminth worm that causes schistosomiasis, catalyzes the conjugation of glutathione with toxic secondary products of membrane lipid peroxidation. Crystal structures of Sj26GST in complex with glutathione sulfonate (Sj26GSTSLF), S-hexyl glutathione (Sj26GSTHEX), and S-2-iodobenzyl glutathione (Sj26GSTIBZ) allow characterization of the electrophile binding site (H site) of Sj26GST. The S-hexyl and S-2-iodobenzyl moieties of these product analogs bind in a pocket defined by side-chains from the beta1-alpha1 loop (Tyr7, Trp8, Ile10, Gly12, Leu13), helix alpha4 (Arg103, Tyr104, Ser107, Tyr111), and the C-terminal coil (Gln204, Gly205, Trp206, Gln207). Changes in the Ser107 and Gln204 dihedral angles make the H site more hydrophobic in the Sj26GSTHEX complex relative to the ligand-free structure. These structures, together with docking studies, indicate a possible binding mode of Sj26GST to its physiologic substrates 4-hydroxynon-2-enal (4HNE), trans-non-2-enal (NE), and ethacrynic acid (EA). In this binding mode, hydrogen bonds of Tyr111 and Gln207 to the carbonyl oxygen atoms of 4HNE, NE, and EA could orient the substrates and enhance their electrophilicity to promote conjugation with glutathione.
来自日本血吸虫（一种导致血吸虫病的蠕虫）的26千道尔顿谷胱甘肽S-转移酶（Sj26GST）催化谷胱甘肽与膜脂过氧化的有毒次级产物的结合。Sj26GST与谷胱甘肽磺酸盐（Sj26GSTSLF）、S-己基谷胱甘肽（Sj26GSTHEX）和S-2-碘苄基谷胱甘肽（Sj26GSTIBZ）形成复合物的晶体结构，使得能够对Sj26GST的亲电试剂结合位点（H位点）进行表征。这些产物类似物的S-己基和S-2-碘苄基部分结合在一个由β1-α1环（Tyr7、Trp8、Ile10、Gly12、Leu13）、α4螺旋（Arg103、Tyr104、Ser107、Tyr111）和C末端卷曲（Gln204、Gly205、Trp206、Gln207）的侧链所界定的口袋中。相对于无配体结构，Ser107和Gln204二面角的变化使得Sj26GSTHEX复合物中的H位点更具疏水性。这些结构以及对接研究表明了Sj26GST与其生理底物4-羟基壬-2-烯醛（4HNE）、反式壬-2-烯醛（NE）和依他尼酸（EA）的一种可能结合模式。在这种结合模式中，Tyr111和Gln207与4HNE、NE和EA的羰基氧原子之间的氢键可以使底物定向并增强其亲电性，以促进与谷胱甘肽的结合。
