4L5M

Complexe of ARNO Sec7 domain with the protein-protein interaction inhibitor N-(4-hydroxy-2,6-dimethylphenyl)benzenesulfonamide at pH6.5

4L5M の概要

• エントリーDOI: 10.2210/pdb4l5m/pdb
• 関連するPDBエントリー: 4JHX 4JMI 4JMO 4JWL
• 分子名称: Cytohesin-2, PHOSPHATE ION, N-(4-hydroxy-2,6-dimethylphenyl)benzenesulfonamide, ... (4 entities in total)
• 機能のキーワード: sec-7domain, signaling protein-inhibitor complex, signaling protein/inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane: Q99418
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25290.72

構造登録者

Hoh, F.,Rouhana, J. (登録日: 2013-06-11, 公開日: 2013-10-30, 最終更新日: 2024-05-29)

主引用文献

Rouhana, J.,Hoh, F.,Estaran, S.,Henriquet, C.,Boublik, Y.,Kerkour, A.,Trouillard, R.,Martinez, J.,Pugniere, M.,Padilla, A.,Chavanieu, A.
Fragment-based identification of a locus in the Sec7 domain of Arno for the design of protein-protein interaction inhibitors.
J.Med.Chem., 56:8497-8511, 2013

PubMed Abstract: By virtual screening using a fragment-based drug design (FBDD) approach, 33 fragments were selected within small pockets around interaction hot spots on the Sec7 surface of the nucleotide exchange factor Arno, and then their ability to interfere with the Arno-catalyzed nucleotide exchange on the G-protein Arf1 was evaluated. By use of SPR, NMR, and fluorescence assays, the direct binding of three of the identified fragments to Arno Sec7 domain was demonstrated and the promiscuous aggregate behavior evaluated. Then the binding mode of one fragment and of a more active analogue was solved by X-ray crystallography. This highlighted the role of stable and transient pockets at the Sec7 domain surface in the discovery and binding of interfering compounds. These results provide structural information on how small organic compounds can interfere with the Arf1-Arno Sec7 domain interaction and may guide the rational drug design of competitive inhibitors of Arno enzymatic activity.

PubMed: 24112024
DOI: 10.1021/jm4009357

実験手法

X-RAY DIFFRACTION (1.8 Å)