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| | ==Crystal Structure of a five site mutated Cyanovirin-N== | | ==Crystal Structure of a five site mutated Cyanovirin-N== |
| - | <StructureSection load='2z21' size='340' side='right' caption='[[2z21]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='2z21' size='340' side='right'caption='[[2z21]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2z21]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Anabaena_variabilis_var._ellipsospora Anabaena variabilis var. ellipsospora]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z21 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Z21 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2z21]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nostoc_ellipsosporum Nostoc ellipsosporum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z21 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2pys|2pys]], [[1lom|1lom]], [[1m5m|1m5m]], [[2ezm|2ezm]], [[1iiy|1iiy]], [[1l5e|1l5e]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cyanovirin-N ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=45916 Anabaena variabilis var. ellipsospora])</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=2z21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z21 OCA], [https://pdbe.org/2z21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z21 RCSB], [https://www.ebi.ac.uk/pdbsum/2z21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z21 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2z21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z21 OCA], [http://pdbe.org/2z21 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2z21 RCSB], [http://www.ebi.ac.uk/pdbsum/2z21 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CVN_NOSEL CVN_NOSEL]] Mannose-binding lectin.<ref>PMID:9210678</ref> <ref>PMID:12678493</ref> | + | [https://www.uniprot.org/uniprot/CVN_NOSEL CVN_NOSEL] Mannose-binding lectin.<ref>PMID:9210678</ref> <ref>PMID:12678493</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z2/2z21_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z2/2z21_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Anabaena variabilis var. ellipsospora]] | + | [[Category: Large Structures]] |
| - | [[Category: Fromme, P]] | + | [[Category: Nostoc ellipsosporum]] |
| - | [[Category: Fromme, R]] | + | [[Category: Fromme P]] |
| - | [[Category: Ghirlanda, G]] | + | [[Category: Fromme R]] |
| - | [[Category: Katilene, Z]] | + | [[Category: Ghirlanda G]] |
| - | [[Category: Anti-hiv]]
| + | [[Category: Katilene Z]] |
| - | [[Category: Cyanovirin-n]]
| + | |
| - | [[Category: Gp120]]
| + | |
| - | [[Category: Sugar binding protein]]
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| Structural highlights
Function
CVN_NOSEL Mannose-binding lectin.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Cyanovirin-N (CV-N) is a 101 amino acid cyanobacterial lectin with potent antiviral activity against HIV, mediated by high-affinity binding to branched N-linked oligomannosides on the viral surface envelope protein gp120. The protein contains two carbohydrate-binding domains, A and B, each of which binds short oligomannosides independently in vitro. The interaction to gp120 could involve either a single domain or both domains simultaneously; it is not clear which mode would elicit the antiviral activity. The model is complicated by the formation of a domain-swapped dimer form, in which part of each domain is exchanged between two monomers, which contains four functional carbohydrate-binding domains. To clarify whether multivalent interactions with gp120 are necessary for the antiviral activity, we engineered a novel mutant, P51G-m4-CVN, in which the binding site on domain A has been knocked out; in addition, a [P51G] mutation prevents the formation of domain-swapped dimers under physiological conditions. Here, we present the crystal structures at 1.8 A of the free and of the dimannose-bound forms of P51G-m4-CVN, revealing a monomeric structure in which only domain B is bound to dimannose. P51G-m4-CVN binds gp120 with an affinity almost 2 orders of magnitude lower than wt CV-N and is completely inactive against HIV. The tight binding to gp120 is recovered in the domain-swapped version of P51G-m4-CVN, prepared under extreme conditions. Our findings show that the presence of at least two oligomannoside-binding sites, either by the presence of intact domains A and B or by formation of domain-swapped dimers, is essential for activity.
A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity.,Fromme R, Katiliene Z, Giomarelli B, Bogani F, Mc Mahon J, Mori T, Fromme P, Ghirlanda G Biochemistry. 2007 Aug 14;46(32):9199-207. Epub 2007 Jul 18. PMID:17636873[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Boyd MR, Gustafson KR, McMahon JB, Shoemaker RH, O'Keefe BR, Mori T, Gulakowski RJ, Wu L, Rivera MI, Laurencot CM, Currens MJ, Cardellina JH 2nd, Buckheit RW Jr, Nara PL, Pannell LK, Sowder RC 2nd, Henderson LE. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrob Agents Chemother. 1997 Jul;41(7):1521-30. PMID:9210678
- ↑ Botos I, Wlodawer A. Cyanovirin-N: a sugar-binding antiviral protein with a new twist. Cell Mol Life Sci. 2003 Feb;60(2):277-87. PMID:12678493
- ↑ Fromme R, Katiliene Z, Giomarelli B, Bogani F, Mc Mahon J, Mori T, Fromme P, Ghirlanda G. A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity. Biochemistry. 2007 Aug 14;46(32):9199-207. Epub 2007 Jul 18. PMID:17636873 doi:10.1021/bi700666m
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