3i97

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{{Seed}}
 
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[[Image:3i97.png|left|200px]]
 
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==B1 domain of human Neuropilin-1 bound with small molecule EG00229==
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The line below this paragraph, containing "STRUCTURE_3i97", creates the "Structure Box" on the page.
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<StructureSection load='3i97' size='340' side='right'caption='[[3i97]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3i97]] is a 2 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=3I97 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I97 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8DR:(S)-2-(3-(BENZO[C][1,2,5]THIADIAZOLE-4-SULFONAMIDO)THIOPHENE-2-CARBOXAMIDO)-5-GUANIDINOPENTANOIC+ACID'>8DR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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{{STRUCTURE_3i97| PDB=3i97 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3i97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i97 OCA], [https://pdbe.org/3i97 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i97 RCSB], [https://www.ebi.ac.uk/pdbsum/3i97 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i97 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NRP1_HUMAN NRP1_HUMAN] The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF-165 isoform of VEGF and VEGF-B. Coexpression with KDR results in increased VEGF-165 binding to KDR as well as increased chemotaxis. It may regulate VEGF-induced angiogenesis. The soluble isoform 2 binds VEGF-165 and appears to inhibit its binding to cells. It may also induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i9/3i97_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3i97 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===B1 domain of human Neuropilin-1 bound with small molecule EG00229===
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Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction.,Jarvis A, Allerston CK, 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 PC, Zachary I, Selwood DL J Med Chem. 2010 Feb 12. PMID:20151671<ref>PMID:20151671</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3i97" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20151671}}, adds the Publication Abstract to the page
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*[[Neuropilin|Neuropilin]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20151671 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20151671}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3I97 is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I97 OCA].
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==Reference==
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<ref group="xtra">PMID:20151671</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Allerston, C K.]]
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[[Category: Large Structures]]
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[[Category: Djordjevic, S.]]
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[[Category: Allerston CK]]
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[[Category: Alternative splicing]]
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[[Category: Djordjevic S]]
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[[Category: Angiogenesis]]
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[[Category: Cell membrane]]
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[[Category: Developmental protein]]
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[[Category: Differentiation]]
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[[Category: Disulfide bond]]
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[[Category: Drug]]
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[[Category: Glycoprotein]]
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[[Category: Heparan sulfate]]
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[[Category: Membrane]]
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[[Category: Membrane protein]]
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[[Category: Neurogenesis]]
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[[Category: Neuropilin]]
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[[Category: Neuropilin-1]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Proteoglycan]]
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[[Category: Receptor]]
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[[Category: Secreted]]
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[[Category: Signaling protein]]
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[[Category: Transmembrane]]
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[[Category: Vegf]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 28 11:19:06 2010''
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Current revision

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

PDB ID 3i97

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