2zfc

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[[Image:2zfc.jpg|left|200px]]
 
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==X-ray crystal structure of an engineered N-terminal HIV-1 GP41 trimer with enhanced stability and potency==
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The line below this paragraph, containing "STRUCTURE_2zfc", creates the "Structure Box" on the page.
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<StructureSection load='2zfc' size='340' side='right'caption='[[2zfc]], [[Resolution|resolution]] 1.50&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'>[[2zfc]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZFC FirstGlance]. <br>
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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]] 1.5&#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=2zfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zfc OCA], [https://pdbe.org/2zfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zfc RCSB], [https://www.ebi.ac.uk/pdbsum/2zfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zfc ProSAT]</span></td></tr>
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{{STRUCTURE_2zfc| PDB=2zfc | SCENE= }}
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</table>
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'''X-ray crystal structure of an engineered N-terminal HIV-1 GP41 trimer with enhanced stability and potency'''
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==See Also==
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*[[Gp41 3D Structures|Gp41 3D Structures]]
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__TOC__
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==Overview==
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</StructureSection>
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HIV fusion is mediated by a conformational transition in which the C-terminal region (HR2) of gp41 interacts with the N-terminal region (HR1) to form a six-helix bundle. Peptides derived from the HR1 form a well-characterized, trimeric coiled-coil bundle in the presence of HR2 peptides, but there is little structural information on the isolated HR1 trimer. Using protein design, we have designed synthetic HR1 peptides that form soluble, thermostable HR1 trimers. In vitro binding of HR2 peptides to the engineered trimer suggests that the design strategy has not significantly impacted the ability to form the six-helix bundle. The peptides have enhanced antiviral activity compared to wild type, with up to 30-fold greater potency against certain viral isolates. In vitro passaging was used to generate HR1-resistant virus and the observed resistance mutations map to the HR2 region of gp41, demonstrating that the peptides block the fusion process by binding to the viral HR2 domain. Interestingly, the activity of the HR2 fusion inhibitor, enfuvirtide (ENF), against these resistant viruses is maintained or improved up to fivefold. The 1.5 A crystal structure of one of these designs has been determined, and we show that the isolated HR1 is very similar to the conformation of the HR1 in the six-helix bundle. These results provide an initial model of the pre-fusogenic state, are attractive starting points for identifying novel fusion inhibitors, and offer new opportunities for developing HIV therapeutics based on HR1 peptides.
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[[Category: Large Structures]]
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[[Category: Dwyer JJ]]
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==About this Structure==
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[[Category: Hasan A]]
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2ZFC is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZFC OCA].
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[[Category: Kim H]]
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[[Category: Martin K]]
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==Reference==
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[[Category: Seedorff JE]]
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Design of an engineered N-terminal HIV-1 gp41 trimer with enhanced stability and potency., Dwyer JJ, Wilson KL, Martin K, Seedorff JE, Hasan A, Medinas RJ, Davison DK, Feese MD, Richter HT, Kim H, Matthews TJ, Delmedico MK, Protein Sci. 2008 Apr;17(4):633-43. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18359857 18359857]
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[[Category: Wilson KL]]
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[[Category: Single protein]]
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[[Category: Dwyer, J J.]]
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[[Category: Hasan, A.]]
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[[Category: Kim, H.]]
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[[Category: Martin, K.]]
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[[Category: Seedorff, J E.]]
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[[Category: Wilson, K L.]]
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[[Category: Gp41]]
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[[Category: Hiv-1]]
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[[Category: Peptide]]
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[[Category: Viral protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:46:24 2008''
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X-ray crystal structure of an engineered N-terminal HIV-1 GP41 trimer with enhanced stability and potency

PDB ID 2zfc

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