Sortase Transpeptidases: Structural Biology and Catalytic Mechanism.
Sortase Transpeptidases: Structural Biology and Catalytic Mechanism.
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DOI：
10.1016/bs.apcsb.2017.04.008
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发表时间：
2017
影响因子：
--
通讯作者：
Clubb RT
中科院分区：
文献类型：
--
作者：
Jacobitz AW;Kattke MD;Wereszczynski J;Clubb RT
革兰氏阳性细菌使用分选酶半胱氨酸转肽酶将蛋白质共价连接到其细胞壁并组装皮利。在病原菌中，分选酶是潜在的药物靶标，因为它们在微生物表面上展示的许多蛋白质在感染过程中起关键作用。此外，金黄色葡萄球菌分选酶A（SaSrtA）酶由于其在体外通过共价肽键将生物分子连接在一起的能力而被开发成有价值的生化试剂。本文综述了分选酶的结构和催化机制。基于它们的一级序列，大多数分选酶同源物可以分为六个不同的亚家族，称为A-F类酶。原子结构揭示了支持替代底物特异性的独特的类特异性变化，而结合到分选信号模拟物的分选酶的结构揭示了底物识别的分子基础。计算研究的结果进行审查，提供洞察关键反应中间体是如何稳定在催化过程中，以及底物识别的机制和动力学。最后，报道的分选酶的体外活性进行比较，揭示了SaSrtA的转肽活性比迄今为止已经表征的其他分选酶快至少20倍。总之，结构，计算，和生化研究中讨论的结果，在这篇评论开始，揭示如何分选酶装饰的微生物表面的蛋白质和皮利，并可能促进正在进行的努力，发现治疗上有用的小分子抑制剂。
Gram-positive bacteria use sortase cysteine transpeptidase enzymes to covalently attach proteins to their cell wall and to assemble pili. In pathogenic bacteria sortases are potential drug targets, as many of the proteins that they display on the microbial surface play key roles in the infection process. Moreover, the Staphylococcus aureus Sortase A (SaSrtA) enzyme has been developed into a valuable biochemical reagent because of its ability to ligate biomolecules together in vitro via a covalent peptide bond. Here we review what is known about the structures and catalytic mechanism of sortase enzymes. Based on their primary sequences, most sortase homologs can be classified into six distinct subfamilies, called class A–F enzymes. Atomic structures reveal unique, class-specific variations that support alternate substrate specificities, while structures of sortase enzymes bound to sorting signal mimics shed light onto the molecular basis of substrate recognition. The results of computational studies are reviewed that provide insight into how key reaction intermediates are stabilized during catalysis, as well as the mechanism and dynamics of substrate recognition. Lastly, the reported in vitro activities of sortases are compared, revealing that the transpeptidation activity of SaSrtA is at least 20-fold faster than other sortases that have thus far been characterized. Together, the results of the structural, computational, and biochemical studies discussed in this review begin to reveal how sortases decorate the microbial surface with proteins and pili, and may facilitate ongoing efforts to discover therapeutically useful small molecule inhibitors.
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影响因子：
4.8
作者：
Jacobitz, Alex W.;Wereszczynski, Jeff;Clubb, Robert T.
通讯作者：
Clubb, Robert T.
DOI：
10.1073/pnas.1101046108
发表时间：
2011-07-12
影响因子：
11.1
作者：
Chen, Irwin;Dorr, Brent M.;Liu, David R.
通讯作者：
Liu, David R.
影响因子：
4.8
作者：
Bentley, Matthew L.;Gaweska, Helena;McCafferty, Dewey G.
通讯作者：
McCafferty, Dewey G.
影响因子：
4.8
作者：
Chan, Albert H.;Yi, Sung Wook;Clubb, Robert T.
通讯作者：
Clubb, Robert T.
影响因子：
2.9
作者：
Huang, XY;Aulabaugh, A;Ellestad, G
通讯作者：
Ellestad, G