1inx

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{{Seed}}
 
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[[Image:1inx.png|left|200px]]
 
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==A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES==
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The line below this paragraph, containing "STRUCTURE_1inx", creates the "Structure Box" on the page.
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<StructureSection load='1inx' size='340' side='right'caption='[[1inx]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1inx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1INX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1INX FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EQP:(4-ACETAMIDO-2,4-DIDEOXY-D-GLYCERO-ALPHA-D-GALACTO-1-OCTOPYRANOSYL)PHOSPHONIC+ACID'>EQP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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{{STRUCTURE_1inx| PDB=1inx | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1inx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1inx OCA], [https://pdbe.org/1inx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1inx RCSB], [https://www.ebi.ac.uk/pdbsum/1inx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1inx ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NRAM_I67A0 NRAM_I67A0] Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/in/1inx_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1inx ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by ePANA was approximately a 100-fold better than by sialic acid, but inhibition of type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound was not a strong inhibitor for any of the NA strains tested. The crystal structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9) NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of the PANA compounds distorted the NA active site upon binding. No significant differences in the NA-ePANA complex structures were found to explain the anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis that an increase in the ePANA inhibition compared to that caused by sialic acid is due to (1) a stronger electrostatic interaction between the inhibitor phosphonyl group and the active site arginine pocket and (2) a lower distortion energy requirement for binding of ePANA.
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===A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES===
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A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.,White CL, Janakiraman MN, Laver WG, Philippon C, Vasella A, Air GM, Luo M J Mol Biol. 1995 Feb 3;245(5):623-34. PMID:7844831<ref>PMID:7844831</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1inx" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_7844831}}, adds the Publication Abstract to the page
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*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 7844831 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_7844831}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Influenza A virus]]
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1INX is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1INX OCA].
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[[Category: Large Structures]]
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[[Category: Air GM]]
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==Reference==
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[[Category: Janakiraman MN]]
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<ref group="xtra">PMID:7844831</ref><references group="xtra"/>
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[[Category: Laver WG]]
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[[Category: Exo-alpha-sialidase]]
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[[Category: Luo M]]
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[[Category: Influenza a virus]]
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[[Category: Philippon C]]
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[[Category: Air, G M.]]
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[[Category: Vasella A]]
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[[Category: Janakiraman, M N.]]
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[[Category: White CL]]
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[[Category: Laver, W G.]]
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[[Category: Luo, M.]]
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[[Category: Philippon, C.]]
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[[Category: Vasella, A.]]
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[[Category: White, C L.]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 16:02:40 2009''
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Current revision

A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES

PDB ID 1inx

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