1l7h

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[[Image:1l7h.gif|left|200px]]
 
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{{Structure
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==Crystal structure of R292K mutant influenza virus neuraminidase in complex with BCX-1812==
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|PDB= 1l7h |SIZE=350|CAPTION= <scene name='initialview01'>1l7h</scene>, resolution 1.85&Aring;
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<StructureSection load='1l7h' size='340' side='right'caption='[[1l7h]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <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>
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<table><tr><td colspan='2'>[[1l7h]] 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=1L7H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L7H FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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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]] 1.85&#8491;</td></tr>
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|GENE=
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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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|DOMAIN=
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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=1l7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l7h OCA], [https://pdbe.org/1l7h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l7h RCSB], [https://www.ebi.ac.uk/pdbsum/1l7h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l7h ProSAT]</span></td></tr>
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|RELATEDENTRY=[[2qwe|2QWE]], [[2qwh|2QWH]], [[1l7f|1L7F]], [[1l7g|1L7G]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l7h OCA], [http://www.ebi.ac.uk/pdbsum/1l7h PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1l7h RCSB]</span>
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== Function ==
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}}
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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/l7/1l7h_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=1l7h ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of R292K mutant influenza virus neuraminidase in complex with BCX-1812'''
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==See Also==
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*[[Neuraminidase 3D structures|Neuraminidase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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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[[Category: Influenza A virus]]
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[[Category: Large Structures]]
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==About this Structure==
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[[Category: Colman PM]]
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1L7H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L7H OCA].
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[[Category: Fernley RT]]
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[[Category: McDonald M]]
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==Reference==
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[[Category: McKimm-Breshkin JL]]
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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://www.ncbi.nlm.nih.gov/pubmed/12014958 12014958]
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[[Category: Smith BJ]]
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[[Category: Exo-alpha-sialidase]]
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[[Category: Varghese JN]]
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[[Category: Single protein]]
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[[Category: Unidentified influenza virus]]
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[[Category: Colman, P M.]]
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[[Category: Fernley, R T.]]
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[[Category: McDonald, M.]]
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[[Category: McKimm-Breshkin, J L.]]
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[[Category: Smith, B J.]]
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[[Category: Varghese, J N.]]
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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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[[Category: r292k mutant]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:59:10 2008''
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Current revision

Crystal structure of R292K mutant influenza virus neuraminidase in complex with BCX-1812

PDB ID 1l7h

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