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Preparation and crystallization of the Grb7 SH2 domain in complex with the G7‐18NATE nonphosphorylated cyclic inhibitor peptide

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Grb7 is an adapter protein that is involved in signalling pathways that mediate eukaryotic cell proliferation and migration. Its overexpression in several cancer types has implicated it in cancer progression and led to the development of the G7‐18NATE cyclic peptide inhibitor. Here, the preparation of crystals of G7‐18NATE in complex with its Grb7 SH2 domain target is reported. Crystals of the complex were grown by the hanging‐drop vapour‐diffusion method using PEG 3350 as the precipitant at room temperature. X‐ray diffraction data were collected from crystals to 2.4 Å resolution using synchrotron X‐ray radiation at 100 K. The diffraction was consistent with space group P21, with unit‐cell parameters a = 52.7, b = 79.1, c = 54.7 Å, α = γ = 90.0, β = 104.4°. The structure of the G7‐18NATE peptide in complex with its target will facilitate the rational development of Grb7‐targeted cancer therapeutics.
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Keywords: G7‐18NATE; Grb7; SH2 domains; inhibitors

Document Type: Research Article

Publication date: December 1, 2010

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