Crystal structure of Staphylococcus aureus metallopeptidase (Sapep) reveals large domain motions between the manganese-bound and apo-states.
Crystal structure of Staphylococcus aureus metallopeptidase (Sapep) reveals large domain motions between the manganese-bound and apo-states.
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DOI：
10.1074/jbc.m110.147579
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发表时间：
2010-09-17
期刊：
影响因子：
--
通讯作者：
Gopal B
中科院分区：
文献类型：
--
作者：
Girish TS;Gopal B
属于M20家族的蛋白水解酶具有不同的底物特异性，参与多种代谢途径。金黄色葡萄球菌金属肽酶SAPEP是氨基酰基酶-I/M20蛋白家族中的一员。该蛋白是一种依赖于Mn2+的二肽酶。该蛋白的晶体结构以Mn2+结合的形式存在，并且处于开放的无金属状态，这表明较大的结构域间运动可能调节该酶的活性。我们注意到扩展的非活性构象是由活性中心附近的二硫键稳定的。虽然这些半胱氨酸，Cys155和Cys178，不是活性位点残基，但这种酶的还原形式作为二肽酶的活性要高得多。这些发现获得了进一步的相关性，因为最近的一项观察表明，这种酶只在耐甲氧西林的金黄色葡萄球菌中有效。这种酶的结构和生化特征为设计新型的耐甲氧西林金黄色葡萄球菌特异性治疗药物提供了模板。
Proteases belonging to the M20 family are characterized by diverse substrate specificity and participate in several metabolic pathways. The Staphylococcus aureus metallopeptidase, Sapep, is a member of the aminoacylase-I/M20 protein family. This protein is a Mn2+-dependent dipeptidase. The crystal structure of this protein in the Mn2+-bound form and in the open, metal-free state suggests that large interdomain movements could potentially regulate the activity of this enzyme. We note that the extended inactive conformation is stabilized by a disulfide bond in the vicinity of the active site. Although these cysteines, Cys155 and Cys178, are not active site residues, the reduced form of this enzyme is substantially more active as a dipeptidase. These findings acquire further relevance given a recent observation that this enzyme is only active in methicillin-resistant S. aureus. The structural and biochemical features of this enzyme provide a template for the design of novel methicillin-resistant S. aureus-specific therapeutics.