Structural genomics of protein phosphatases

Structural genomics of protein phosphatases
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DOI:
10.1007/s10969-007-9036-1
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发表时间:
2007-09-01
期刊:
Journal of Structural and Functional Genomics
影响因子:
--
通讯作者:
Burley, Stephen K.
Burley, Stephen K.
中科院分区:
其他
文献类型:
--
作者:
Almo, Steven C.;Bonanno, Jeffrey B.;Burley, Stephen K.

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美国国立综合医学科学研究所(NIGMS)蛋白质结构倡议(PSI)的纽约结构基因组学SGX研究中心(NYSGXRC)已将其高通量X射线晶体学结构测定平台应用于对所有人类蛋白磷酸酶以及来自生物医学相关病原体的蛋白磷酸酶的系统研究。到目前为止,NYSGXRC已经测定了21种不同蛋白磷酸酶的结构:14种来自人类,2种来自小鼠,2种来自病原体刚地弓形虫,1种来自布氏锥虫(导致非洲昏睡病的寄生虫),还有2种来自非洲疟疾的主要蚊媒冈比亚按蚊。这些结构为正常和病理生理过程提供了见解,包括转录调控、主要信号通路的调控、神经发育以及1型糖尿病。与其他国际结构基因组学联盟的贡献相结合,这些努力有望为所有类别蛋白磷酸酶抑制剂的结构导向实验和计算发现提供一个前所未有的数据库和材料库。
The New York SGX Research Center for Structural Genomics (NYSGXRC) of the NIGMS Protein Structure Initiative (PSI) has applied its high-throughput X-ray crystallographic structure determination platform to systematic studies of all human protein phosphatases and protein phosphatases from biomedically-relevant pathogens. To date, the NYSGXRC has determined structures of 21 distinct protein phosphatases: 14 from human, 2 from mouse, 2 from the pathogen Toxoplasma gondii, 1 from Trypanosoma brucei, the parasite responsible for African sleeping sickness, and 2 from the principal mosquito vector of malaria in Africa, Anopheles gambiae. These structures provide insights into both normal and pathophysiologic processes, including transcriptional regulation, regulation of major signaling pathways, neural development, and type 1 diabetes. In conjunction with the contributions of other international structural genomics consortia, these efforts promise to provide an unprecedented database and materials repository for structure-guided experimental and computational discovery of inhibitors for all classes of protein phosphatases.