Suppr超能文献

人类双特异性磷酸酶7的结构,一种潜在的癌症药物靶点。

Structure of human dual-specificity phosphatase 7, a potential cancer drug target.

作者信息

Lountos George T, Austin Brian P, Tropea Joseph E, Waugh David S

机构信息

Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, PO Box B, Frederick, MD 21702, USA.

出版信息

Acta Crystallogr F Struct Biol Commun. 2015 Jun;71(Pt 6):650-6. doi: 10.1107/S2053230X1500504X. Epub 2015 May 20.

Abstract

Human dual-specificity phosphatase 7 (DUSP7/Pyst2) is a 320-residue protein that belongs to the mitogen-activated protein kinase phosphatase (MKP) subfamily of dual-specificity phosphatases. Although its precise biological function is still not fully understood, previous reports have demonstrated that DUSP7 is overexpressed in myeloid leukemia and other malignancies. Therefore, there is interest in developing DUSP7 inhibitors as potential therapeutic agents, especially for cancer. Here, the purification, crystallization and structure determination of the catalytic domain of DUSP7 (Ser141-Ser289/C232S) at 1.67 Å resolution are reported. The structure described here provides a starting point for structure-assisted inhibitor-design efforts and adds to the growing knowledge base of three-dimensional structures of the dual-specificity phosphatase family.

摘要

人双特异性磷酸酶7(DUSP7/Pyst2)是一种由320个氨基酸残基组成的蛋白质,属于双特异性磷酸酶的丝裂原活化蛋白激酶磷酸酶(MKP)亚家族。尽管其确切的生物学功能仍未完全明确,但先前的报道表明,DUSP7在髓系白血病和其他恶性肿瘤中过表达。因此,人们有兴趣开发DUSP7抑制剂作为潜在的治疗药物,尤其是用于癌症治疗。在此,报道了DUSP7催化结构域(Ser141-Ser289/C232S)在1.67 Å分辨率下的纯化、结晶及结构测定。此处描述的结构为基于结构的抑制剂设计工作提供了一个起点,并丰富了双特异性磷酸酶家族三维结构的知识储备。

相似文献

1
Structure of human dual-specificity phosphatase 7, a potential cancer drug target.人类双特异性磷酸酶7的结构,一种潜在的癌症药物靶点。
Acta Crystallogr F Struct Biol Commun. 2015 Jun;71(Pt 6):650-6. doi: 10.1107/S2053230X1500504X. Epub 2015 May 20.
4
Crystal structure of a novel mitogen-activated protein kinase phosphatase, SKRP1.
Proteins. 2011 Nov;79(11):3242-6. doi: 10.1002/prot.23156. Epub 2011 Aug 30.
7
The family-wide structure and function of human dual-specificity protein phosphatases.人类双特异性蛋白磷酸酶的全家族结构与功能
Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):421-35. doi: 10.1107/S1399004713029866. Epub 2014 Jan 29.

本文引用的文献

1
Protein tyrosine phosphatases as potential therapeutic targets.蛋白酪氨酸磷酸酶作为潜在的治疗靶点。
Acta Pharmacol Sin. 2014 Oct;35(10):1227-46. doi: 10.1038/aps.2014.80. Epub 2014 Sep 15.
2
The family-wide structure and function of human dual-specificity protein phosphatases.人类双特异性蛋白磷酸酶的全家族结构与功能
Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):421-35. doi: 10.1107/S1399004713029866. Epub 2014 Jan 29.
4
The MORPHEUS protein crystallization screen.MORPHEUS蛋白质结晶筛选
J Appl Crystallogr. 2009 Dec 1;42(Pt 6):1035-1042. doi: 10.1107/S0021889809042022. Epub 2009 Nov 7.
7
REFMAC5 for the refinement of macromolecular crystal structures.用于大分子晶体结构精修的REFMAC5
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67. doi: 10.1107/S0907444911001314. Epub 2011 Mar 18.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验