6eku: Difference between revisions
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==Vibrio cholerae neuraminidase complexed with zanamivir== | ==Vibrio cholerae neuraminidase complexed with zanamivir== | ||
<StructureSection load='6eku' size='340' side='right' caption='[[6eku]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='6eku' size='340' side='right'caption='[[6eku]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6eku]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EKU OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[6eku]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibch Vibch]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EKU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6EKU FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZMR:ZANAMIVIR'>ZMR</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZMR:ZANAMIVIR'>ZMR</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nanH, VC_1784 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243277 VIBCH])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6eku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eku OCA], [http://pdbe.org/6eku PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eku RCSB], [http://www.ebi.ac.uk/pdbsum/6eku PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eku ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6eku" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6eku" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Exo-alpha-sialidase]] | [[Category: Exo-alpha-sialidase]] | ||
[[Category: Large Structures]] | |||
[[Category: Vibch]] | |||
[[Category: Heinemann, U]] | [[Category: Heinemann, U]] | ||
[[Category: Schuetz, A]] | [[Category: Schuetz, A]] | ||
Latest revision as of 12:12, 11 November 2020
Vibrio cholerae neuraminidase complexed with zanamivirVibrio cholerae neuraminidase complexed with zanamivir
Structural highlights
Function[NANH_VIBCH] Cleaves the terminal sialic acid (N-acetyl neuraminic acid) from carbohydrate chains in glycoproteins providing free sialic acid which can be used as carbon and energy sources. Sialidases have been suggested to be pathogenic factors in microbial infections. Facilitates cholera toxin binding to host intestinal epithelial cells by converting cell surface polysialogangliosides to GM1 monogangliosides. Publication Abstract from PubMedNeuraminidaseis a key enzyme in the life cycle of influenza viruses and is present in some bacterial pathogens. We here assess the inhibitory potency of plant tannins versus clinically used inhibitors on both a viral and a bacterial model neuraminidase by applying the 2'-(4-methylumbelliferyl)-alpha-d-N-acetylneuraminic acid (MUNANA)-based activity assay. A range of flavan-3-ols, ellagitannins and chemically defined proanthocyanidin fractions was evaluated in comparison to oseltamivir carboxylate and zanamivir for their inhibitory activities against viral influenza A (H1N1) and bacterial Vibrio cholerae neuraminidase (VCNA). Compared to the positive controls, all tested polyphenols displayed a weak inhibition of the viral enzyme but similar or even higher potency on the bacterial neuraminidase. Structure-activity relationship analyses revealed the presence of galloyl groups and the hydroxylation pattern of the flavan skeleton to be crucial for inhibitory activity. The combination of zanamivir and EPs((R)) 7630 (root extract of Pelargonium sidoides) showed synergistic inhibitory effects on the bacterial neuraminidase. Co-crystal structures of VCNA with oseltamivir carboxylate and zanamivir provided insight into bacterial versus viral enzyme-inhibitor interactions. The current data clearly indicate that inhibitor potency strongly depends on the biological origin of the enzyme and that results are not readily transferable. The therapeutic relevance of our findings is briefly discussed. Different Inhibitory Potencies of Oseltamivir Carboxylate, Zanamivir, and Several Tannins on Bacterial and Viral Neuraminidases as Assessed in a Cell-Free Fluorescence-Based Enzyme Inhibition Assay.,Quosdorf S, Schuetz A, Kolodziej H Molecules. 2017 Nov 17;22(11). pii: molecules22111989. doi:, 10.3390/molecules22111989. PMID:29149072[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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