Oakley A J, Lo Bello M, Nuccetelli M, Mazzetti A P, Parker M W
The Ian Potter Foundation Protein Crystallography Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, Victoria, 3065, Australia.
J Mol Biol. 1999 Aug 27;291(4):913-26. doi: 10.1006/jmbi.1999.3029.
Glutathione S -transferases (GSTs) play a pivotal role in the detoxification of foreign chemicals and toxic metabolites. They were originally termed ligandins because of their ability to bind large molecules (molecular masses >400 Da), possibly for storage and transport roles. The location of the ligandin site in mammalian GSTs is still uncertain despite numerous studies in recent years. Here we show by X-ray crystallography that the ligandin binding site in human pi class GST P1-1 occupies part of one of the substrate binding sites. This work has been extended to the determination of a number of enzyme complex crystal structures which show that very large ligands are readily accommodated into this substrate binding site and in all, but one case, causes no significant movement of protein side-chains. Some of these molecules make use of a hitherto undescribed binding site located in a surface pocket of the enzyme. This site is conserved in most, but not all, classes of GSTs suggesting it may play an important functional role.
谷胱甘肽S-转移酶（GSTs）在对外源化学物质和有毒代谢产物的解毒过程中起着关键作用。它们最初被称为配体蛋白，因为它们能够结合大分子（分子量>400 Da），可能具有储存和运输功能。尽管近年来进行了大量研究，但哺乳动物GSTs中配体蛋白位点的位置仍不确定。在这里，我们通过X射线晶体学表明，人π类GST P1-1中的配体蛋白结合位点占据了一个底物结合位点的一部分。这项工作已扩展到多个酶复合物晶体结构的测定，结果表明非常大的配体很容易容纳到这个底物结合位点中，并且除了一个案例外，在所有情况下都不会导致蛋白质侧链的显著移动。其中一些分子利用了位于酶表面口袋中的一个迄今未描述的结合位点。这个位点在大多数但不是所有类别的GSTs中是保守的，这表明它可能发挥重要的功能作用。
