标题:Crystal Structure and Substrate Specificity of PTPN12
作者:Li, Hui; Yang, Fan; Liu, Chunhua; Xiao, Peng; Xu, Yunfei; Liang, Zonglai; Liu, Chuan; Wang, Hongmei; Wang, Wenjun; Zheng, Wenshuai; 更多
作者机构:[Li, Hui; Yang, Fan; Liu, Chunhua; Liang, Zonglai; Wang, Hongmei; Wang, Wenjun; Zheng, Wenshuai; Zhang, Wei; Ma, Xiaoyun; He, Dongfang; Yu, Xiao] Shan 更多
通讯作者:Yu, X;Yu, X;Sun, JP
通讯作者地址:[Yu, X]Shandong Univ, Sch Med, Minist Educ, Key Lab Expt Teratol, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China;[Yu, X]Shandong Univ, Sch M 更多
来源:CELL REPORTS
出版年:2016
卷:15
期:6
页码:1345-1358
DOI:10.1016/j.celrep.2016.04.016
摘要:PTPN12 is an important tumor suppressor that plays critical roles in various physiological processes. However, the molecular basis underlying the substrate specificity of PTPN12 remains uncertain. Here, enzymological and crystallographic studies have enabled us to identify two distinct structural features that are crucial determinants of PTPN12 substrate specificity: the pY+1 site binding pocket and specific basic charged residues along its surface loops. Key structurally plastic regions and specific residues in PTPN12 enabled recognition of different HER2 phosphorylation sites and regulated specific PTPN12 functions. In addition, the structure of PTPN12 revealed a CDK2 phosphorylation site in a specific PTPN12 loop. Taken together, our results not only provide the working mechanisms of PTPN12 for desphosphorylation of its substrates but will also help in designing specific inhibitors of PTPN12.
收录类别:SCOPUS;SCIE
WOS核心被引频次:7
Scopus被引频次:7
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84964642997&doi=10.1016%2fj.celrep.2016.04.016&partnerID=40&md5=63eb9992366e97937e34f50068704221
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