Ambaye Nigus D, Gunzburg Menachem J, Traore Daouda A K, Del Borgo Mark P, Perlmutter Patrick, Wilce Matthew C J, Wilce Jacqueline A
Department of Biochemistry and Molecular Biology, Monash University, VIC 3800, Australia.
School of Chemistry, Monash University, VIC 3800, Australia.
Acta Crystallogr F Struct Biol Commun. 2014 Feb;70(Pt 2):182-6. doi: 10.1107/S2053230X13033414. Epub 2014 Jan 21.
Human growth factor receptor-bound protein 7 (Grb7) is an adapter protein involved in cell growth, migration and proliferation. It is now recognized that Grb7 is an emerging therapeutic target in specific cancer subtypes. Recently, the discovery of a bicyclic peptide inhibitor that targets the Grb7 SH2 domain, named G7-B1, was reported. In an attempt to probe the foundation of its interaction with Grb7, the crystallization and preliminary data collection of both the apo and G7-B1-bound forms of the Grb7 SH2 domain are reported here. Diffraction-quality crystals were obtained using the hanging-drop vapour-diffusion method. After several rounds of microseeding, crystals of the apo Grb7 SH2 domain were obtained that diffracted to 1.8 Å resolution, while those of the G7-B1-Grb7 SH2 domain complex diffracted to 2.2 Å resolution. The apo Grb7 SH2 domain crystallized in the trigonal space group P63, whereas the G7-B1-Grb7 SH2 domain complex crystallized in the monoclinic space group P21. The experimental aspects of crystallization, crystal optimization and data collection and the preliminary data are reported.
人生长因子受体结合蛋白7（Grb7）是一种参与细胞生长、迁移和增殖的衔接蛋白。现在人们认识到，Grb7是特定癌症亚型中一个新出现的治疗靶点。最近，有报道称发现了一种靶向Grb7 SH2结构域的双环肽抑制剂，名为G7-B1。为了探究其与Grb7相互作用的基础，本文报道了Grb7 SH2结构域的无配体形式和与G7-B1结合形式的结晶及初步数据收集情况。采用悬滴气相扩散法获得了衍射质量良好的晶体。经过几轮微种子接种，获得了无配体Grb7 SH2结构域的晶体，其衍射分辨率达到1.8 Å，而G7-B1-Grb7 SH2结构域复合物的晶体衍射分辨率为2.2 Å。无配体Grb7 SH2结构域在三方晶系空间群P63中结晶，而G7-B1-Grb7 SH2结构域复合物在单斜晶系空间群P21中结晶。本文报道了结晶、晶体优化、数据收集的实验情况以及初步数据。
