The ATP-grasp enzymes.
The ATP-grasp enzymes.
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DOI：
10.1016/j.bioorg.2011.08.004
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发表时间：
2011-12
影响因子：
5.1
通讯作者：
Firestine SM
中科院分区：
文献类型：
--
作者：
Fawaz MV;Topper ME;Firestine SM
atp抓取酶由21个蛋白质组成的超家族组成，这些蛋白质包含一个非典型的atp结合位点，称为atp抓取折叠。ATP抓握折叠由两个α + β结构域组成，它们在它们之间“抓握”ATP分子，家族成员通常具有包含3个共同保守焦点结构域的整体结构设计。该家族的创始成员包括生物素羧化酶、D-ala-D-ala连接酶和谷胱甘肽合成酶，它们都通过形成酰基磷酸中间体来催化atp辅助羧酸与亲核试剂的反应。虽然超家族的大多数成员遵循这一机制途径，但研究表明，有两种酶仅催化磷酸化转移步骤，因此是激酶而不是连接酶。ATP-grasp超家族的成员在一些代谢途径中被发现，包括从头嘌呤生物合成、糖异生和脂肪酸合成。鉴于这些酶的关键性质，研究人员积极寻求开发超家族成员的有效抑制剂，作为抗菌和抗肥胖剂。本文就atp抓取酶的结构、功能、作用机制及其抑制作用进行综述。
The ATP-grasp enzymes consist of a superfamily of 21 proteins that contain an atypical ATP-binding site, called the ATP-grasp fold. The ATP-grasp fold is comprised of two α + β domains that “grasp” a molecule of ATP between them and members of the family typically have an overall structural design containing 3 common conserved focal domains. The founding members of the family consist of biotin carboxylase, D-ala-D-ala ligase and glutathione synthetase, all of which catalyze the ATP-assisted reaction of a carboxylic acid with a nucleophile via the formation of an acylphosphate intermediate. While most members of the superfamily follow this mechanistic pathway, studies have demonstrated that two enzymes catalyze only the phosphoryl transfer step and thus are kinases instead of ligases. Members of the ATP-grasp superfamily are found in several metabolic pathways including de novo purine biosynthesis, gluconeogenesis and fatty acid synthesis. Given the critical nature of these enzymes, researchers have actively sought the development of potent inhibitors of several members of the superfamily as antibacterial and anti-obseity agents. In this review, we will discuss the structure, function, mechanism and inhibition of the ATP-grasp enzymes.