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| | ==Crystal structure of 2009 pandemic H1N1 neuraminidase complexed with laninamivir== | | ==Crystal structure of 2009 pandemic H1N1 neuraminidase complexed with laninamivir== |
| - | <StructureSection load='3ti3' size='340' side='right' caption='[[3ti3]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3ti3' size='340' side='right'caption='[[3ti3]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ti3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/I09a0 I09a0]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TI3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TI3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ti3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/California/04/2009(H1N1)) Influenza A virus (A/California/04/2009(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TI3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LNV:5-(ACETYLAMINO)-2,6-ANHYDRO-4-CARBAMIMIDAMIDO-3,4,5-TRIDEOXY-7-O-METHYL-D-GLYCERO-D-GALACTO-NON-2-ENONIC+ACID'>LNV</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nss|3nss]], [[3ti4|3ti4]], [[3ti5|3ti5]], [[3ti6|3ti6]], [[3ti8|3ti8]], [[3tia|3tia]], [[3tib|3tib]], [[3tic|3tic]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LNV:5-(ACETYLAMINO)-2,6-ANHYDRO-4-CARBAMIMIDAMIDO-3,4,5-TRIDEOXY-7-O-METHYL-D-GLYCERO-D-GALACTO-NON-2-ENONIC+ACID'>LNV</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=641501 I09A0])</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=3ti3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ti3 OCA], [https://pdbe.org/3ti3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ti3 RCSB], [https://www.ebi.ac.uk/pdbsum/3ti3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ti3 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=3ti3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ti3 OCA], [http://pdbe.org/3ti3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ti3 RCSB], [http://www.ebi.ac.uk/pdbsum/3ti3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ti3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/C3W5S3_I09A0 C3W5S3_I09A0] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Neuraminidase|Neuraminidase]] | + | *[[Neuraminidase 3D structures|Neuraminidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: I09a0]] | + | [[Category: Large Structures]] |
| - | [[Category: Feng, E]] | + | [[Category: Feng E]] |
| - | [[Category: Gao, F]] | + | [[Category: Gao F]] |
| - | [[Category: Gao, G F]] | + | [[Category: Gao GF]] |
| - | [[Category: He, J]] | + | [[Category: He J]] |
| - | [[Category: Jiang, H]] | + | [[Category: Jiang H]] |
| - | [[Category: Li, Q]] | + | [[Category: Li Q]] |
| - | [[Category: Liu, H]] | + | [[Category: Liu H]] |
| - | [[Category: Liu, J]] | + | [[Category: Liu J]] |
| - | [[Category: Liu, Y]] | + | [[Category: Liu Y]] |
| - | [[Category: Qi, J]] | + | [[Category: Qi J]] |
| - | [[Category: Vavricka, C J]] | + | [[Category: Vavricka CJ]] |
| - | [[Category: Wang, J]] | + | [[Category: Wang J]] |
| - | [[Category: Wang, M]] | + | [[Category: Wang M]] |
| - | [[Category: Wu, Y]] | + | [[Category: Wu Y]] |
| - | [[Category: 6-bladed beta-propeller]]
| + | |
| - | [[Category: Antiviral]]
| + | |
| - | [[Category: Calcium binding]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
3ti3 is a 2 chain structure with sequence from Influenza A virus (A/California/04/2009(H1N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.8Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
C3W5S3_I09A0
Publication Abstract from PubMed
The 2009 H1N1 influenza pandemic (pH1N1) led to record sales of neuraminidase (NA) inhibitors, which has contributed significantly to the recent increase in oseltamivir-resistant viruses. Therefore, development and careful evaluation of novel NA inhibitors is of great interest. Recently, a highly potent NA inhibitor, laninamivir, has been approved for use in Japan. Laninamivir is effective using a single inhaled dose via its octanoate prodrug (CS-8958) and has been demonstrated to be effective against oseltamivir-resistant NA in vitro. However, effectiveness of laninamivir octanoate prodrug against oseltamivir-resistant influenza infection in adults has not been demonstrated. NA is classified into 2 groups based upon phylogenetic analysis and it is becoming clear that each group has some distinct structural features. Recently, we found that pH1N1 N1 NA (p09N1) is an atypical group 1 NA with some group 2-like features in its active site (lack of a 150-cavity). Furthermore, it has been reported that certain oseltamivir-resistant substitutions in the NA active site are group 1 specific. In order to comprehensively evaluate the effectiveness of laninamivir, we utilized recombinant N5 (typical group 1), p09N1 (atypical group 1) and N2 from the 1957 pandemic H2N2 (p57N2) (typical group 2) to carry out in vitro inhibition assays. We found that laninamivir and its octanoate prodrug display group specific preferences to different influenza NAs and provide the structural basis of their specific action based upon their novel complex crystal structures. Our results indicate that laninamivir and zanamivir are more effective against group 1 NA with a 150-cavity than group 2 NA with no 150-cavity. Furthermore, we have found that the laninamivir octanoate prodrug has a unique binding mode in p09N1 that is different from that of group 2 p57N2, but with some similarities to NA-oseltamivir binding, which provides additional insight into group specific differences of oseltamivir binding and resistance.
Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza na inhibition.,Vavricka CJ, Li Q, Wu Y, Qi J, Wang M, Liu Y, Gao F, Liu J, Feng E, He J, Wang J, Liu H, Jiang H, Gao GF PLoS Pathog. 2011 Oct;7(10):e1002249. Epub 2011 Oct 20. PMID:22028647[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Vavricka CJ, Li Q, Wu Y, Qi J, Wang M, Liu Y, Gao F, Liu J, Feng E, He J, Wang J, Liu H, Jiang H, Gao GF. Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza na inhibition. PLoS Pathog. 2011 Oct;7(10):e1002249. Epub 2011 Oct 20. PMID:22028647 doi:10.1371/journal.ppat.1002249
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