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| - | [[Image:1w0o.gif|left|200px]] | |
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| - | <!-- | + | ==Vibrio cholerae sialidase== |
| - | The line below this paragraph, containing "STRUCTURE_1w0o", creates the "Structure Box" on the page.
| + | <StructureSection load='1w0o' size='340' side='right'caption='[[1w0o]], [[Resolution|resolution]] 1.90Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1w0o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0O FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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=DAN:2-DEOXY-2,3-DEHYDRO-N-ACETYL-NEURAMINIC+ACID'>DAN</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr> |
| - | {{STRUCTURE_1w0o| PDB=1w0o | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0o OCA], [https://pdbe.org/1w0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0o RCSB], [https://www.ebi.ac.uk/pdbsum/1w0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0o ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NANH_VIBCH 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. |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Vibrio cholerae neuraminidase (VCNA) plays a significant role in the pathogenesis of cholera by removing sialic acid from higher order gangliosides to unmask GM1, the receptor for cholera toxin. We previously showed that the structure of VCNA is composed of a central beta-propeller catalytic domain flanked by two lectin-like domains; however the nature of the carbohydrates recognized by these lectin domains has remained unknown. We present here structures of the enzyme in complex with two substrates, alpha-2,3-sialyllactose and alpha-2,6-sialyllactose. Both substrate complexes reveal the alpha-anomer of N-acetylneuraminic acid (Neu5Ac) bound to the N-terminal lectin domain, thereby revealing the role of this domain. The large number of interactions suggest a relatively high binding affinity for sialic acid, which was confirmed by calorimetry, which gave a Kd approximately 30 microm. Saturation transfer difference NMR using a non-hydrolyzable substrate, Neu5,9Ac2-2-S-(alpha-2,6)-GlcNAcbeta1Me, was also used to map the ligand interactions at the VCNA lectin binding site. It is well known that VCNA can hydrolyze both alpha-2,3- and alpha-2,6-linked sialic acid substrates. In this study using alpha-2,3-sialyllactose co-crystallized with VCNA it was revealed that the inhibitor 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en) was bound at the catalytic site. This observation supports the notion that VCNA can produce its own inhibitor and has been further confirmed by 1H NMR analysis. The discovery of the sialic acid binding site in the N-lectin-like domain suggests that this might help target VCNA to sialic acid-rich environments, thereby enhancing the catalytic efficiency of the enzyme. |
| | | | |
| - | '''VIBRIO CHOLERAE SIALIDASE'''
| + | Sialic acid recognition by Vibrio cholerae neuraminidase.,Moustafa I, Connaris H, Taylor M, Zaitsev V, Wilson JC, Kiefel MJ, von Itzstein M, Taylor G J Biol Chem. 2004 Sep 24;279(39):40819-26. Epub 2004 Jun 28. PMID:15226294<ref>PMID:15226294</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 1w0o" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | Vibrio cholerae neuraminidase (VCNA) plays a significant role in the pathogenesis of cholera by removing sialic acid from higher order gangliosides to unmask GM1, the receptor for cholera toxin. We previously showed that the structure of VCNA is composed of a central beta-propeller catalytic domain flanked by two lectin-like domains; however the nature of the carbohydrates recognized by these lectin domains has remained unknown. We present here structures of the enzyme in complex with two substrates, alpha-2,3-sialyllactose and alpha-2,6-sialyllactose. Both substrate complexes reveal the alpha-anomer of N-acetylneuraminic acid (Neu5Ac) bound to the N-terminal lectin domain, thereby revealing the role of this domain. The large number of interactions suggest a relatively high binding affinity for sialic acid, which was confirmed by calorimetry, which gave a Kd approximately 30 microm. Saturation transfer difference NMR using a non-hydrolyzable substrate, Neu5,9Ac2-2-S-(alpha-2,6)-GlcNAcbeta1Me, was also used to map the ligand interactions at the VCNA lectin binding site. It is well known that VCNA can hydrolyze both alpha-2,3- and alpha-2,6-linked sialic acid substrates. In this study using alpha-2,3-sialyllactose co-crystallized with VCNA it was revealed that the inhibitor 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en) was bound at the catalytic site. This observation supports the notion that VCNA can produce its own inhibitor and has been further confirmed by 1H NMR analysis. The discovery of the sialic acid binding site in the N-lectin-like domain suggests that this might help target VCNA to sialic acid-rich environments, thereby enhancing the catalytic efficiency of the enzyme.
| + | *[[Neuraminidase 3D structures|Neuraminidase 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 1W0O is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0O OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | [[Category: Large Structures]] |
| - | Sialic acid recognition by Vibrio cholerae neuraminidase., Moustafa I, Connaris H, Taylor M, Zaitsev V, Wilson JC, Kiefel MJ, von Itzstein M, Taylor G, J Biol Chem. 2004 Sep 24;279(39):40819-26. Epub 2004 Jun 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15226294 15226294]
| + | |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Vibrio cholerae]]
| + | |
| - | [[Category: Connaris, H.]]
| + | |
| - | [[Category: Kiefel, M J.]]
| + | |
| - | [[Category: Moustafa, I.]]
| + | |
| - | [[Category: Taylor, G.]]
| + | |
| - | [[Category: Taylor, M.]]
| + | |
| - | [[Category: Von-Itzstein, M.]]
| + | |
| - | [[Category: Wilson, J C.]]
| + | |
| - | [[Category: Zaitsev, V.]]
| + | |
| - | [[Category: Glycosidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Sialidase]] | + | |
| | [[Category: Vibrio cholerae]] | | [[Category: Vibrio cholerae]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:59:58 2008''
| + | [[Category: Connaris H]] |
| | + | [[Category: Kiefel MJ]] |
| | + | [[Category: Moustafa I]] |
| | + | [[Category: Taylor G]] |
| | + | [[Category: Taylor M]] |
| | + | [[Category: Wilson JC]] |
| | + | [[Category: Zaitsev V]] |
| | + | [[Category: Von-Itzstein M]] |
| 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 PubMed
Vibrio cholerae neuraminidase (VCNA) plays a significant role in the pathogenesis of cholera by removing sialic acid from higher order gangliosides to unmask GM1, the receptor for cholera toxin. We previously showed that the structure of VCNA is composed of a central beta-propeller catalytic domain flanked by two lectin-like domains; however the nature of the carbohydrates recognized by these lectin domains has remained unknown. We present here structures of the enzyme in complex with two substrates, alpha-2,3-sialyllactose and alpha-2,6-sialyllactose. Both substrate complexes reveal the alpha-anomer of N-acetylneuraminic acid (Neu5Ac) bound to the N-terminal lectin domain, thereby revealing the role of this domain. The large number of interactions suggest a relatively high binding affinity for sialic acid, which was confirmed by calorimetry, which gave a Kd approximately 30 microm. Saturation transfer difference NMR using a non-hydrolyzable substrate, Neu5,9Ac2-2-S-(alpha-2,6)-GlcNAcbeta1Me, was also used to map the ligand interactions at the VCNA lectin binding site. It is well known that VCNA can hydrolyze both alpha-2,3- and alpha-2,6-linked sialic acid substrates. In this study using alpha-2,3-sialyllactose co-crystallized with VCNA it was revealed that the inhibitor 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en) was bound at the catalytic site. This observation supports the notion that VCNA can produce its own inhibitor and has been further confirmed by 1H NMR analysis. The discovery of the sialic acid binding site in the N-lectin-like domain suggests that this might help target VCNA to sialic acid-rich environments, thereby enhancing the catalytic efficiency of the enzyme.
Sialic acid recognition by Vibrio cholerae neuraminidase.,Moustafa I, Connaris H, Taylor M, Zaitsev V, Wilson JC, Kiefel MJ, von Itzstein M, Taylor G J Biol Chem. 2004 Sep 24;279(39):40819-26. Epub 2004 Jun 28. PMID:15226294[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Moustafa I, Connaris H, Taylor M, Zaitsev V, Wilson JC, Kiefel MJ, von Itzstein M, Taylor G. Sialic acid recognition by Vibrio cholerae neuraminidase. J Biol Chem. 2004 Sep 24;279(39):40819-26. Epub 2004 Jun 28. PMID:15226294 doi:10.1074/jbc.M404965200
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