An overview of the protein tyrosine phosphatase superfamily.
An overview of the protein tyrosine phosphatase superfamily.
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DOI：
10.2174/1568026033452302
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发表时间：
2003-02
影响因子：
3.4
通讯作者：
Wei-qing Wang;Jin-Peng Sun;Zhon-Yin Zhang
中科院分区：
文献类型：
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作者：
Wei-qing Wang;Jin-Peng Sun;Zhon-Yin Zhang
人类基因组编码大约100种属于蛋白酪氨酸磷酸酶（PTP）超家族的磷酸酶，其底物范围从蛋白质到磷酸肌醇和mRNA。这个超家族的标志是活性位点序列C（X）5 R，也称为PTP签名基序。PTP是信号转导途径中的关键调节组分，并且PTP在细胞信号传导控制中的重要性已得到充分确立。此外，有令人信服的理由相信PTP抑制剂可以作为治疗各种疾病的新型药物。基于结构和底物特异性，PTP超家族分为四个不同的亚家族：1）。pTyr特异性PTP，2）。双特异性磷酸酶，3）。Cdc 25磷酸酶，和4）。低分子量PTPs。PTP具有类似的核心结构，由中心平行β-折叠和侧翼α-螺旋组成，所述α-螺旋含有包含PTP特征基序的β-环-α环。毫不奇怪，尽管底物特异性不同，但它们采用共同的磷酸盐水解化学机制。尽管保守的结构和催化性能，也有足够的差异，在不同的PTP之间的活性位点口袋和它的直接周围环境。进一步的结构和机理研究将继续具有相当重要的意义，为抑制剂设计提供坚实的基础。
The human genome encodes approximately 100 phosphatases that belong to the protein tyrosine phosphatase (PTP) superfamily, whose substrates range from proteins to phosphoinositides and mRNAs. The hallmark for this superfamily is the active site sequence C(X)5R, also known as the PTP signature motif. The PTPs are key regulatory components in signal transduction pathways and the importance of PTPs in the control of cellular signaling is well established. Furthermore, there are compelling reasons to believe that PTP inhibitors may serve as novel medicinal agents for the treatment of various diseases. Based on structure and substrate specificity, the PTP super-family is divided into four distinct subfamilies: 1). pTyr specific PTPs, 2). dual specificity phosphatases, 3). Cdc25 phosphatases, and 4). LMW PTPs. The PTPs have similar core structures made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha loop that encompasses the PTP signature motif. Not surprisingly, they employ a common chemical mechanism for phosphate hydrolysis despite the differences in substrate specificity. Despite the conserved structural and catalytic properties, there are also sufficient differences in the active site pockets and its immediate surrounding environment among different PTPs. Further structural and mechanistic study will continue to be of considerable importance, providing a solid basis for inhibitor design.