2vxw

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{{Seed}}
 
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[[Image:2vxw.png|left|200px]]
 
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==Structural and Functional Studies of the Potent Anti-HIV Chemokine Variant P2-RANTES==
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The line below this paragraph, containing "STRUCTURE_2vxw", creates the "Structure Box" on the page.
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<StructureSection load='2vxw' size='340' side='right'caption='[[2vxw]], [[Resolution|resolution]] 1.70&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'>[[2vxw]] is a 4 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=2VXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VXW 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]] 1.7&#8491;</td></tr>
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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=2vxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxw OCA], [https://pdbe.org/2vxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vxw RCSB], [https://www.ebi.ac.uk/pdbsum/2vxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vxw ProSAT]</span></td></tr>
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{{STRUCTURE_2vxw| PDB=2vxw | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CCL5_HUMAN CCL5_HUMAN] Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. Binds to CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils.<ref>PMID:16791620</ref> <ref>PMID:1380064</ref> <ref>PMID:8525373</ref> <ref>PMID:9516414</ref> <ref>PMID:15923218</ref>
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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/vx/2vxw_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=2vxw 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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The N-terminal region of the chemokine RANTES is critical for its function. A synthesized N-terminally modified analog of RANTES, P2-RANTES, was discovered using a phage display selection against living CCR5-expressing cells, and has been reported to inhibit HIV-1 env-mediated cell-cell fusion at subnanomolar levels (Hartley et al. J Virol 2003;77:6637-6644). In the present study we produced this protein using E. coli overexpression and extensively studied its structure and function. The x-ray crystal structure of P2-RANTES was solved and refined at 1.7 A resolution. This protein was found to be predominantly a monomer in solution by analytical ultracentrifugation, but a tetramer in the crystal. In studies of glycosaminoglycan binding, P2-RANTES was found to be significantly less able to bind heparin than wild type RANTES. We also tested this protein for receptor internalization where it was shown to be functional, in cell-cell fusion assays where recombinant P2-RANTES was a potent fusion inhibitor (IC(50) = 2.4 +/- 0.8 nM), and in single round infection assays where P2-RANTES inhibited at subnanomolar levels. Further, in a modified fusion assay designed to test specificity of inhibition, P2-RANTES was also highly effective, with a 65-fold improvement over the fusion inhibitor C37, which is closely related to the clinically approved inhibitor T-20. These studies provide detailed structural and functional information for this novel N-terminally modified chemokine mutant. This information will be very useful in the development of more potent anti-HIV agents. PDB Accession Number: 2vxw. Proteins 2009. (c) 2009 Wiley-Liss, Inc.
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===STRUCTURAL AND FUNCTIONAL STUDIES OF THE POTENT ANTI-HIV CHEMOKINE VARIANT P2-RANTES===
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Structural and functional studies of the potent anti-HIV chemokine variant P2-RANTES.,Jin H, Kagiampakis I, Li P, Liwang PJ Proteins. 2009 Jul 20. PMID:19722264<ref>PMID:19722264</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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==About this Structure==
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</div>
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2VXW is a 4 chains structure of 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=2VXW OCA].
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<div class="pdbe-citations 2vxw" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Jin, H.]]
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[[Category: Large Structures]]
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[[Category: Li, P.]]
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[[Category: Jin H]]
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[[Category: Liwang, P J.]]
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[[Category: Li P]]
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[[Category: Cell-cell fusion]]
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[[Category: LiWang PJ]]
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[[Category: Chemokine]]
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[[Category: Chemotaxis]]
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[[Category: Cytokine]]
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[[Category: Glycoprotein]]
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[[Category: Hiv entry]]
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[[Category: Inflammatory response]]
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[[Category: Polymorphism]]
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[[Category: Secreted]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 05:29:16 2009''
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Current revision

Structural and Functional Studies of the Potent Anti-HIV Chemokine Variant P2-RANTES

PDB ID 2vxw

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