Structure and substrate recognition of the Staphylococcus aureus protein tyrosine phosphatase PtpA.
Structure and substrate recognition of the Staphylococcus aureus protein tyrosine phosphatase PtpA.
复制标题
金黄色葡萄球菌蛋白酪氨酸磷酸酶 PtpA 的结构和底物识别。
DOI：
10.1016/j.jmb.2011.08.015
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发表时间：
2011
影响因子：
5.6
通讯作者：
Grundner,Christoph
中科院分区：
文献类型：
--
作者：
Vega,Carolina;Chou,Seemay;Engel,Katherine;Harrell,MariaE;Rajagopal,Lakshmi;Grundner,Christoph
通过pSer/pThr/pTyr的磷酸化信号传导正在成为原核生物中常见的信号传导机制。人类病原体金黄色葡萄球菌产生两种功能未知的低分子量蛋白酪氨酸磷酸酶（PTPs），PtpA和PtpB。为了提供理解PtpA功能和底物识别的结构背景，建立PtpA在PTP家族中的结构关系，并为设计特异性抑制剂提供框架，我们以1 μ m分辨率解析了PtpA的晶体结构。虽然PtpA采用共同的，保守的PTP折叠，并显示出密切的整体相似性，真核PTP，在活性位点和表面组织的几个功能是独特的，可以探索设计选择性抑制剂。结合在活性位点的肽模拟磷酸酪氨酸底物，提供底物识别的洞察力，并提供可测试的底物预测。ptpA或ptpB的基因缺失不影响体外生长或细胞壁完整性，这增加了PtpA和PtpB在感染期间具有专门功能的可能性。
Phosphosignaling through pSer/pThr/pTyr is emerging as a common signaling mechanism in prokaryotes. The human pathogen Staphylococcus aureus produces two low-molecular-weight protein tyrosine phosphatases (PTPs), PtpA and PtpB, with unknown functions. To provide the structural context for understanding PtpA function and substrate recognition, establish PtpA's structural relations within the PTP family, and provide a framework for the design of specific inhibitors, we solved the crystal structure of PtpA at 1 Å resolution. While PtpA adopts the common, conserved PTP fold and shows close overall similarity to eukaryotic PTPs, several features in the active site and surface organization are unique and can be explored to design selective inhibitors. A peptide bound in the active site mimics a phosphotyrosine substrate, affords insight into substrate recognition, and provides a testable substrate prediction. Genetic deletion of ptpA or ptpB does not affect in vitro growth or cell wall integrity, raising the possibility that PtpA and PtpB have specialized functions during infection.