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==Influenza Neuraminidase in complex with antiviral compound (3S,4R,5R)-4-(acetylamino)-3-carbamimidamido-5-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylic acid== | |||
<StructureSection load='4ks2' size='340' side='right' caption='[[4ks2]], [[Resolution|resolution]] 2.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ks2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/duck/ukraine/1/1963(h3n8)) Influenza a virus (a/duck/ukraine/1/1963(h3n8))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KS2 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1SJ:(3S,4R,5R)-4-(ACETYLAMINO)-3-CARBAMIMIDAMIDO-5-(PENTAN-3-YLOXY)CYCLOHEX-1-ENE-1-CARBOXYLIC+ACID'>1SJ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ks1|4ks1]], [[4ks3|4ks3]], [[4ks4|4ks4]], [[4ks5|4ks5]]</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=385580 Influenza A virus (A/duck/Ukraine/1/1963(H3N8))])</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=4ks2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ks2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ks2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ks2 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The influenza virus neuraminidase (NA) is essential for the virus life cycle. The rise of resistance mutations against current antiviral therapies has increased the need for the development of novel inhibitors. Recent efforts have targeted a cavity adjacent to the catalytic site (the 150-cavity) in addition to the primary catalytic subsite in order to increase specificity and reduce the likelihood of resistance. This study details structural and in vitro analyses of a class of inhibitors that bind uniquely in both subsites. Crystal structures of three inhibitors show occupation of the 150-cavity in two distinct and novel binding modes. We believe these are the first nanomolar inhibitors of NA to be characterized in this way. Furthermore, we show that one inhibitor, binding within the catalytic site, offers reduced susceptibility to known resistance mutations via increased flexibility of a pendant pentyloxy group and the ability to pivot about a strong hydrogen-bonding network. | |||
Structural basis for a class of nanomolar influenza A neuraminidase inhibitors.,Kerry PS, Mohan S, Russell RJ, Bance N, Niikura M, Pinto BM Sci Rep. 2013 Oct 16;3:2871. doi: 10.1038/srep02871. PMID:24129600<ref>PMID:24129600</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: Kerry, P S | |||
[[Category: Russell, R J.M | ==See Also== | ||
*[[Neuraminidase|Neuraminidase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Kerry, P S]] | |||
[[Category: Russell, R J.M]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
[[Category: Sialidase]] | [[Category: Sialidase]] | ||
Revision as of 17:32, 21 December 2014
Influenza Neuraminidase in complex with antiviral compound (3S,4R,5R)-4-(acetylamino)-3-carbamimidamido-5-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylic acidInfluenza Neuraminidase in complex with antiviral compound (3S,4R,5R)-4-(acetylamino)-3-carbamimidamido-5-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylic acid
Structural highlights
Publication Abstract from PubMedThe influenza virus neuraminidase (NA) is essential for the virus life cycle. The rise of resistance mutations against current antiviral therapies has increased the need for the development of novel inhibitors. Recent efforts have targeted a cavity adjacent to the catalytic site (the 150-cavity) in addition to the primary catalytic subsite in order to increase specificity and reduce the likelihood of resistance. This study details structural and in vitro analyses of a class of inhibitors that bind uniquely in both subsites. Crystal structures of three inhibitors show occupation of the 150-cavity in two distinct and novel binding modes. We believe these are the first nanomolar inhibitors of NA to be characterized in this way. Furthermore, we show that one inhibitor, binding within the catalytic site, offers reduced susceptibility to known resistance mutations via increased flexibility of a pendant pentyloxy group and the ability to pivot about a strong hydrogen-bonding network. Structural basis for a class of nanomolar influenza A neuraminidase inhibitors.,Kerry PS, Mohan S, Russell RJ, Bance N, Niikura M, Pinto BM Sci Rep. 2013 Oct 16;3:2871. doi: 10.1038/srep02871. PMID:24129600[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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