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Preparation of crystals for characterizing the Grb7 SH2 domain before and after complex formation with a bicyclic peptide antagonist
Author(s) -
Ambaye Nigus D.,
Gunzburg Menachem J.,
Traore Daouda A. K.,
Del Borgo Mark P.,
Perlmutter Patrick,
Wilce Matthew C. J.,
Wilce Jacqueline A.
Publication year - 2014
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x13033414
Subject(s) - sh2 domain , peptide , materials science , monoclinic crystal system , crystallography , biophysics , chemistry , crystal structure , receptor , proto oncogene tyrosine protein kinase src , biology , biochemistry
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 P 6 3 , whereas the G7‐B1–Grb7 SH2 domain complex crystallized in the monoclinic space group P 2 1 . The experimental aspects of crystallization, crystal optimization and data collection and the preliminary data are reported.