Lountos George T, Austin Brian P, Tropea Joseph E, Waugh David S
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.
Acta Crystallogr F Struct Biol Commun. 2015 Jun;71(Pt 6):650-6. doi: 10.1107/S2053230X1500504X. Epub 2015 May 20.
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.
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。