A mixed disulfide bond in bacterial glutathione transferase: functional and evolutionary implications
A mixed disulfide bond in bacterial glutathione transferase: functional and evolutionary implications
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DOI：
10.1016/s0969-2126(98)00074-4
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发表时间：
1998-06-15
期刊：
影响因子：
--
通讯作者：
Parker, MW
中科院分区：
文献类型：
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作者：
Rossjohn, J;Polekhina, G;Parker, MW
背景：谷胱甘肽S转移酶(GSTs)是一类多功能的酶，广泛存在于好氧生物体内，在细胞解毒过程中起着关键作用。与哺乳动物不同，细菌GST经常催化非常特定的反应，这表明它们在细菌中的作用可能不同。奇异变形杆菌的GST(PmGST B1-1)已知能与某些抗生素紧密结合，降低β-内酰胺类药物的抗菌活性。因此，细菌GST可能在细菌对抗生素的耐药性中发挥作用，并引起人们的极大兴趣。结果：我们提出了一种细菌GST的结构，PmGST B1-1，它是由两种不同的晶型确定的。该酶采用典型的GST折叠，尽管它与高等生物中的GST序列同源性不到20%。该结构最令人惊讶的方面是观察到底物谷胱甘肽与酶的Cys10共价结合。结论：PmGST B1-1的晶体结构突出了半胱氨酸残基在催化循环中的重要性。序列分析表明，许多其他GST也具有这一特性，这导致我们提出了一类新的GST-Beta类。这些数据表明，β类GST在体内的作用可能是作为代谢酶或氧化还原酶，而不是结合酶。令人信服的证据表明，theta类GST是从硫氧还蛋白超家族的一个祖先成员进化而来的。
Background: 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.Results: 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 Cys10 of the enzyme. In addition, the highly structurally conserved N-terminal domain is found to have an additional beta strand.Conclusions: 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.