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1l7f

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(New page: 200px<br /><applet load="1l7f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l7f, resolution 1.80&Aring;" /> '''Crystal structure of...)
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[[Image:1l7f.gif|left|200px]]<br /><applet load="1l7f" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1l7f, resolution 1.80&Aring;" />
 
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'''Crystal structure of influenza virus neuraminidase in complex with BCX-1812'''<br />
 
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==Overview==
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==Crystal structure of influenza virus neuraminidase in complex with BCX-1812==
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Zanamivir and oseltamivir, specific inhibitors of influenza virus, neuraminidase, have significantly different characteristics in resistance, studies. In both cases resistance is known to arise through mutations in, either the hemagglutinin or neuraminidase surface proteins. A new, inhibitor under development by Biocryst Pharmaceuticals, BCX-1812, has, both a guanidino group, as in zanamivir, and a bulky hydrophobic group, as, in oseltamivir. Using influenza A/NWS/Tern/Australia/G70C/75 (H1N9), neuraminidase variants E119G and R292K have previously been selected by, different inhibitors. The sensitivity of these variants to BCX-1812 has, now been measured and found in both cases to be intermediate between those, of zanamivir and oseltamivir. In addition, the X-ray crystal structures of, the complexes of BCX-1812 with the wild type and the two mutant, neuraminidases were determined. The ligand is bound in an identical manner, in each structure, with a rearrangement of the side chain of E276 from its, ligand-free position. A structural explanation of the mechanism of, resistance of BCX-1812, relative to zanamivir and oseltamivir in, particular, is provided.
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<StructureSection load='1l7f' size='340' side='right'caption='[[1l7f]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1l7f]] 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=1L7F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L7F 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]] 1.8&#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=BCZ:3-(1-ACETYLAMINO-2-ETHYL-BUTYL)-4-GUANIDINO-2-HYDROXY-CYCLOPENTANECARBOXYLIC+ACID'>BCZ</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1l7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l7f OCA], [https://pdbe.org/1l7f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l7f RCSB], [https://www.ebi.ac.uk/pdbsum/1l7f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l7f ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NRAM_I75A5 NRAM_I75A5] 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/l7/1l7f_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=1l7f 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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1L7F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus] with NAG, CA, BCZ and GOL 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=1L7F 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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Structural studies of the resistance of influenza virus neuramindase to inhibitors., Smith BJ, McKimm-Breshkin JL, McDonald M, Fernley RT, Varghese JN, Colman PM, J Med Chem. 2002 May 23;45(11):2207-12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12014958 12014958]
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[[Category: Influenza A virus]]
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[[Category: Exo-alpha-sialidase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Colman PM]]
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[[Category: Unidentified influenza virus]]
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[[Category: Fernley RT]]
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[[Category: Colman, P.M.]]
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[[Category: McDonald M]]
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[[Category: Fernley, R.T.]]
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[[Category: McKimm-Breshkin JL]]
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[[Category: McDonald, M.]]
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[[Category: Smith BJ]]
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[[Category: McKimm-Breshkin, J.L.]]
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[[Category: Varghese JN]]
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[[Category: Smith, B.J.]]
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[[Category: Varghese, J.N.]]
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[[Category: BCZ]]
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[[Category: CA]]
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[[Category: GOL]]
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[[Category: NAG]]
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[[Category: bcx-1812]]
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[[Category: glycosylated protein]]
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[[Category: hydrolase]]
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[[Category: influenza]]
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[[Category: n9 neuraminidase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:20:42 2007''
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Current revision

Crystal structure of influenza virus neuraminidase in complex with BCX-1812

PDB ID 1l7f

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