1ive

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(New page: 200px<br /><applet load="1ive" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ive, resolution 2.4&Aring;" /> '''STRUCTURES OF AROMATI...)
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[[Image:1ive.gif|left|200px]]<br /><applet load="1ive" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ive, resolution 2.4&Aring;" />
 
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'''STRUCTURES OF AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE'''<br />
 
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==Overview==
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==STRUCTURES OF AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE==
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Neuraminidase (NA), a surface glycoprotein of influenza virus, is a, potential target for design of antiinfluenza agents. The crystal structure, of influenza virus neuraminidase showed that in the active site 11, residues are universally conserved among all strains known so far. Several, potent inhibitors based on the carbohydrate compound, 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA) have been shown to, bind to the conserved active site and to reduce virus infection in animals, when administered by nasal spray. Inhibitors of this type are, however, rapidly excreted from physiological systems and may not be effective in, order to provide long-time protection. A new class of specific NA, inhibitors, which are benzoic acid derivatives, has been designed on the, basis of the three-dimensional structure of the NA-DANA complex and, modeling of derivatives of 4-(acetylamino)benzoic acid in the NA active, site. Intermediates were synthesized and were shown to moderately inhibit, the NA activity and to bind to the NA active site as predicted. These, rudimentary inhibitors, 4-(acetylamino)-3-hydroxy-5-nitrobenzoic acid, 4-(acetylamino)-3-hydroxy-5-aminobenzoic acid, and, 4-(acetylamino)-3-aminobenzoic acid, and their X-ray structures in, complexes with N2 (A/Tokyo/3/67) and B/Lee/40 neuraminidases have been, analyzed. The coordinates of such inhibitors complexed with NA were used, as the starting model for further design of more potent benzoic acid, inhibitors. Because the active site residues of NA are invariant, the, designed aromatic inhibitors have the potential to become an antiviral, drug against all strains of influenza virus.
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<StructureSection load='1ive' size='340' side='right'caption='[[1ive]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ive]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Tokyo/3/1967(H2N2)) Influenza A virus (A/Tokyo/3/1967(H2N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IVE FirstGlance]. <br>
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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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=ST3:4-(ACETYLAMINO)-3-AMINO+BENZOIC+ACID'>ST3</scene></td></tr>
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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=1ive FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ive OCA], [https://pdbe.org/1ive PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ive RCSB], [https://www.ebi.ac.uk/pdbsum/1ive PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ive 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/iv/1ive_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1ive ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1IVE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with MAN, CA and ST3 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IVE OCA].
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*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structures of aromatic inhibitors of influenza virus neuraminidase., Jedrzejas MJ, Singh S, Brouillette WJ, Laver WG, Air GM, Luo M, Biochemistry. 1995 Mar 14;34(10):3144-51. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7880809 7880809]
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[[Category: Large Structures]]
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[[Category: Exo-alpha-sialidase]]
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[[Category: Jedrzejas MJ]]
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[[Category: Single protein]]
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[[Category: Luo M]]
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[[Category: Jedrzejas, M.J.]]
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[[Category: Luo, M.]]
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[[Category: CA]]
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[[Category: MAN]]
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[[Category: ST3]]
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[[Category: hydrolase (o-glycosyl)]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 17:42:03 2007''
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STRUCTURES OF AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE

PDB ID 1ive

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