Rossjohn J, Polekhina G, Feil S C, Allocati N, Masulli M, Di Illio C, Parker M W
The Ian Potter Foundation Protein Crystallography Laboratory St Vincent's Institute of Medical Research 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia.
Structure. 1998 Jun 15;6(6):721-34. doi: 10.1016/s0969-2126(98)00074-4.
Glutathione S-transferases (GSTs) are a multifunctional group of enzymes, widely distributed in aerobic organisms, that have a critical role in the cellular detoxification process. Unlike their mammalian counterparts, bacterial GSTs often catalyze quite specific reactions, suggesting that their roles in bacteria might be different. The GST from Proteus mirabilis (PmGST B1-1) is known to bind certain antibiotics tightly and reduce the antimicrobial activity of beta-lactam drugs. Hence, bacterial GSTs may play a part in bacterial resistance towards antibiotics and are the subject of intense interest.
Here we present the structure of a bacterial GST, PmGST B1-1, which has been determined from two different crystal forms. The enzyme adopts the canonical GST fold although it shares less than 20% sequence identity with GSTs from higher organisms. The most surprising aspect of the structure is the observation that the substrate, glutathione, is covalently bound to Cys 10 of the enzyme. In addition, the highly structurally conserved N-terminal domain is found to have an additional beta strand.
The crystal structure of PmGST B1-1 has highlighted the importance of a cysteine residue in the catalytic cycle. Sequence analyses suggest that a number of other GSTs share this property, leading us to propose a new class of GSTs - the beta class. The data suggest that the in vivo role of the beta class GSTs could be as metabolic or redox enzymes rather than conjugating enzymes. Compelling evidence is presented that the theta class of GSTs evolved from an ancestral member of the thioredoxin superfamily.
谷胱甘肽S-转移酶（GSTs）是一组多功能酶，广泛分布于需氧生物中，在细胞解毒过程中起关键作用。与哺乳动物的谷胱甘肽S-转移酶不同，细菌的谷胱甘肽S-转移酶通常催化相当特异的反应，这表明它们在细菌中的作用可能有所不同。奇异变形杆菌的谷胱甘肽S-转移酶（PmGST B1-1）已知能紧密结合某些抗生素并降低β-内酰胺类药物的抗菌活性。因此，细菌谷胱甘肽S-转移酶可能在细菌对抗生素的耐药性中起作用，并且是人们密切关注的对象。
在此我们展示了一种细菌谷胱甘肽S-转移酶PmGST B1-1的结构，该结构是通过两种不同的晶体形式确定的。尽管该酶与高等生物的谷胱甘肽S-转移酶的序列同一性不到20%，但它采用了典型的谷胱甘肽S-转移酶折叠结构。该结构最令人惊讶的方面是观察到底物谷胱甘肽与酶的Cys 10共价结合。此外，发现高度保守的N端结构域还有一条额外的β链。
PmGST B1-1的晶体结构突出了催化循环中一个半胱氨酸残基的重要性。序列分析表明，许多其他谷胱甘肽S-转移酶也具有这一特性，这使我们提出了一类新的谷胱甘肽S-转移酶——β类。数据表明，β类谷胱甘肽S-转移酶在体内的作用可能是作为代谢或氧化还原酶，而不是共轭酶。有力证据表明，θ类谷胱甘肽S-转移酶是从硫氧还蛋白超家族的一个祖先成员进化而来的。
