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| | ==Microvirin:mannobiose complex== | | ==Microvirin:mannobiose complex== |
| - | <StructureSection load='2yhh' size='340' side='right'caption='[[2yhh]], [[NMR_Ensembles_of_Models | 2 NMR models]]' scene=''> | + | <StructureSection load='2yhh' size='340' side='right'caption='[[2yhh]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2yhh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Iam_m-247 Iam m-247]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YHH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2yhh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Microcystis_aeruginosa Microcystis aeruginosa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YHH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2y1s|2y1s]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=PRD_900111:2alpha-alpha-mannobiose'>PRD_900111</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=2yhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yhh OCA], [https://pdbe.org/2yhh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yhh RCSB], [https://www.ebi.ac.uk/pdbsum/2yhh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yhh ProSAT]</span></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=2yhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yhh OCA], [https://pdbe.org/2yhh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yhh RCSB], [https://www.ebi.ac.uk/pdbsum/2yhh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yhh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q2MDE2_MICAE Q2MDE2_MICAE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Iam m-247]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bewley, C A]] | + | [[Category: Microcystis aeruginosa]] |
| - | [[Category: Clore, G M]] | + | [[Category: Bewley CA]] |
| - | [[Category: Ghirlando, R]] | + | [[Category: Clore GM]] |
| - | [[Category: Gustchina, E]] | + | [[Category: Ghirlando R]] |
| - | [[Category: Hussan, S]] | + | [[Category: Gustchina E]] |
| - | [[Category: Anti-hiv protein]]
| + | [[Category: Hussan S]] |
| - | [[Category: Cell-cell attachment]]
| + | |
| - | [[Category: Cyanovirin family]]
| + | |
| - | [[Category: Sugar binding protein]]
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| Structural highlights
Function
Q2MDE2_MICAE
Publication Abstract from PubMed
Lectins that bind surface envelope glycoprotein gp120 of HIV with high avidity can potently inhibit viral entry. Yet properties such as multivalency that facilitate strong interactions can also cause nonspecific binding and toxicity. The cyanobacterial lectin microvirin (MVN) is unusual as it potently inhibits HIV-1 with negligible toxicity compared with cyanovirin-N (CVN), its well studied antiviral homolog. To understand the structural and mechanistic basis for these differences, we solved the solution structure of MVN free and in complex with its ligand Manalpha(1-2)Man, and we compared specificity and time windows of inhibition with CVN and Manalpha(1-2)Man-specific mAb 2G12. We show by NMR and analytical ultracentrifugation that MVN is monomeric in solution, and we demonstrate by NMR that Manalpha(1-2)Man-terminating carbohydrates interact with a single carbohydrate-binding site. Synchronized infectivity assays show that 2G12, MVN, and CVN inhibit entry with distinct kinetics. Despite shared specificity for Manalpha(1-2)Man termini, combinations of the inhibitors are synergistic suggesting they recognize discrete glycans and/or dynamic glycan conformations on gp120. Entry assays employing amphotropic viruses show that MVN is inactive, whereas CVN potently inhibits both. In addition to demonstrating that HIV-1 can be inhibited through monovalent interactions, given the similarity of the carbohydrate-binding site common to MVN and CVN, these data suggest that gp120 behaves as a clustered glycan epitope and that multivalent-protein interactions achievable with CVN but not MVN are required for inhibition of some viruses.
Solution structure of the monovalent lectin microvirin in complex with Man(alpha)(1-2)Man provides a basis for anti-HIV activity with low toxicity.,Shahzad-ul-Hussan S, Gustchina E, Ghirlando R, Clore GM, Bewley CA J Biol Chem. 2011 Jun 10;286(23):20788-96. Epub 2011 Apr 6. PMID:21471192[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shahzad-ul-Hussan S, Gustchina E, Ghirlando R, Clore GM, Bewley CA. Solution structure of the monovalent lectin microvirin in complex with Man(alpha)(1-2)Man provides a basis for anti-HIV activity with low toxicity. J Biol Chem. 2011 Jun 10;286(23):20788-96. Epub 2011 Apr 6. PMID:21471192 doi:10.1074/jbc.M111.232678
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