4JWL
Complexe of ARNO Sec7 domain with the protein-protein interaction inhibitor N-(4-hydroxy-2,6-dimethylphenyl)benzenesulfonamide at pH7.5
Summary for 4JWL
| Entry DOI | 10.2210/pdb4jwl/pdb |
| Related | 4JMI 4JMO 4JXH 4L5M |
| Descriptor | Cytohesin-2, N-(4-hydroxy-2,6-dimethylphenyl)benzenesulfonamide (3 entities in total) |
| Functional Keywords | signaling protein, arf1, signaling protein-inhibitor complex, signaling protein/inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell membrane; Peripheral membrane protein: Q99418 |
| Total number of polymer chains | 1 |
| Total formula weight | 25195.75 |
| Authors | Hoh, F.,Rouhana, J. (deposition date: 2013-03-27, release date: 2013-10-23, Last modification date: 2023-11-08) |
| Primary citation | 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 Cited by 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: 24112024DOI: 10.1021/jm4009357 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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