3I97

B1 domain of human Neuropilin-1 bound with small molecule EG00229

3I97 の概要

• エントリーDOI: 10.2210/pdb3i97/pdb
• 分子名称: Neuropilin-1, (S)-2-(3-(benzo[c][1,2,5]thiadiazole-4-sulfonamido)thiophene-2-carboxamido)-5-guanidinopentanoic acid, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: neuropilin-1, drug, vegf, angiogenesis, neuropilin, alternative splicing, cell membrane, developmental protein, differentiation, disulfide bond, glycoprotein, heparan sulfate, membrane, neurogenesis, phosphoprotein, polymorphism, proteoglycan, receptor, secreted, transmembrane, membrane protein, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: O14786
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36921.82

構造登録者

Allerston, C.K.,Djordjevic, S. (登録日: 2009-07-10, 公開日: 2010-03-02, 最終更新日: 2024-11-20)

主引用文献

Jarvis, A.,Allerston, C.K.,Jia, H.,Herzog, B.,Garza-Garcia, A.,Winfield, N.,Ellard, K.,Aqil, R.,Lynch, R.,Chapman, C.,Hartzoulakis, B.,Nally, J.,Stewart, M.,Cheng, L.,Menon, M.,Tickner, M.,Djordjevic, S.,Driscoll, P.C.,Zachary, I.,Selwood, D.L.
Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction.
J.Med.Chem., 53:2215-2226, 2010

PubMed Abstract: We report the molecular design and synthesis of EG00229, 2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural characterization of NRP1-ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis studies localized VEGF-A binding in the NRP1 b1 domain and a peptide fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells was also observed. The viability of A549 lung carcinoma cells was reduced by 2, and it increased the potency of the cytotoxic agents paclitaxel and 5-fluorouracil when given in combination. These studies provide the basis for design of specific small molecule inhibitors of ligand binding to NRP1.

PubMed: 20151671
DOI: 10.1021/jm901755g

実験手法

X-RAY DIFFRACTION (2.9 Å)