7MPH
GRB2 SH2 Domain with Compound 7
Summary for 7MPH
| Entry DOI | 10.2210/pdb7mph/pdb |
| Descriptor | Growth factor receptor-bound protein 2, (4-{(10R,11E,14S,18S)-18-(2-amino-2-oxoethyl)-14-[(naphthalen-1-yl)methyl]-8,17,20-trioxo-7,16,19-triazaspiro[5.14]icos-11-en-10-yl}phenyl)acetic acid, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | inhibitor, complex, growth factor receptor, ras-mapk signaling cascade, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 6 |
| Total formula weight | 71830.90 |
| Authors | Sun, L.,Schonbrunn, E. (deposition date: 2021-05-04, release date: 2021-09-22, Last modification date: 2023-10-18) |
| Primary citation | Xiao, T.,Sun, L.,Zhang, M.,Li, Z.,Haura, E.B.,Schonbrunn, E.,Ji, H. Synthesis and structural characterization of a monocarboxylic inhibitor for GRB2 SH2 domain. Bioorg.Med.Chem.Lett., 51:128354-128354, 2021 Cited by PubMed Abstract: A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction (PPI) between GRB2 and phosphotyrosine-containing proteins. Biochemical characterizations show compound 7 binds with the Src homology 2 (SH2) domain of GRB2 and is more potent than EGFR phosphopeptide 14-mer. X-ray crystallographic studies demonstrate compound 7 occupies the GRB2 binding site for phosphotyrosine-containing sequences and reveal key structural features for GRB2-inhibitor binding. This compound with a -1 formal charge offers a new direction for structural optimization to generate cell-permeable inhibitors for this key protein target of the aberrant Ras-MAPK signaling cascade. PubMed: 34506932DOI: 10.1016/j.bmcl.2021.128354 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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