4l5m
From Proteopedia
(Difference between revisions)
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==Complexe of ARNO Sec7 domain with the protein-protein interaction inhibitor N-(4-hydroxy-2,6-dimethylphenyl)benzenesulfonamide at pH6.5== | ==Complexe of ARNO Sec7 domain with the protein-protein interaction inhibitor N-(4-hydroxy-2,6-dimethylphenyl)benzenesulfonamide at pH6.5== | ||
| - | <StructureSection load='4l5m' size='340' side='right'caption='[[4l5m]]' scene=''> | + | <StructureSection load='4l5m' size='340' side='right'caption='[[4l5m]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L5M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L5M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4l5m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L5M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L5M FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4l5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l5m OCA], [https://pdbe.org/4l5m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l5m RCSB], [https://www.ebi.ac.uk/pdbsum/4l5m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l5m ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HRC:N-(4-HYDROXY-2,6-DIMETHYLPHENYL)BENZENESULFONAMIDE'>HRC</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4l5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l5m OCA], [https://pdbe.org/4l5m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l5m RCSB], [https://www.ebi.ac.uk/pdbsum/4l5m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l5m ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CYH2_HUMAN CYH2_HUMAN] Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane.<ref>PMID:17398095</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. Using 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. | ||
| + | |||
| + | Fragment-Based Identification of a Locus in the Sec7 Domain of Arno for the Design of Protein-Protein Interaction Inhibitors.,Jad R, Hoh F, Estaran S, Henriquet C, Boublik Y, Kerkour A, Trouillard R, Martinez J, Pugniere M, Padilla A, Chavanieu A J Med Chem. 2013 Oct 11. PMID:24112024<ref>PMID:24112024</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4l5m" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hoh F]] | [[Category: Hoh F]] | ||
[[Category: Rouhana J]] | [[Category: Rouhana J]] | ||
Current revision
Complexe of ARNO Sec7 domain with the protein-protein interaction inhibitor N-(4-hydroxy-2,6-dimethylphenyl)benzenesulfonamide at pH6.5
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