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| | <StructureSection load='1vcj' size='340' side='right'caption='[[1vcj]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='1vcj' size='340' side='right'caption='[[1vcj]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1vcj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_b_virus_(b/lee/40) Influenza b virus (b/lee/40)]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1uja 1uja]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VCJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VCJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1vcj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_b_virus_(b/lee/40) Influenza b virus (b/lee/40)]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1uja 1uja]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VCJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IBA:4-[(2R)-2-(AMINOMETHYL)-2-(HYDROXYMETHYL)-5-OXOPYRROLIDIN-1-YL]-3-[(1-ETHYLPROPYL)AMINO]BENZOIC+ACID'>IBA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IBA:4-[(2R)-2-(AMINOMETHYL)-2-(HYDROXYMETHYL)-5-OXOPYRROLIDIN-1-YL]-3-[(1-ETHYLPROPYL)AMINO]BENZOIC+ACID'>IBA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] </span></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=1vcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vcj OCA], [http://pdbe.org/1vcj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vcj RCSB], [http://www.ebi.ac.uk/pdbsum/1vcj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1vcj ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1vcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vcj OCA], [https://pdbe.org/1vcj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vcj RCSB], [https://www.ebi.ac.uk/pdbsum/1vcj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vcj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NRAM_INBLE NRAM_INBLE]] 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 (By similarity). | + | [[https://www.uniprot.org/uniprot/NRAM_INBLE NRAM_INBLE]] 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 (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Structural highlights
Function
[NRAM_INBLE] 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 (By similarity).
Publication Abstract from PubMed
Owing to the highly conserved nature of its active site, Influenza B virus neuraminidase (NA) has emerged as a major target for the design of novel anti-influenza drugs. A benzene-ring scaffold has been used in place of the pyranose ring of sialic acid to develop simpler NA inhibitors that contain a minimal number of chiral centers. A new compound belonging to this series, BANA 207, showed significant improvement in inhibitory activity against Influenza B virus NA compared with its parent compound. Here, the structural analysis of a complex of BANA 207 with influenza virus B/Lee/40 NA is reported. The results indicate that BANA 207 forms an unexpected interaction with the crucial active-site residue Glu275 that stabilizes the side chain of this residue in a conformation previously unobserved in NA-inhibitor complexes. This change in the side-chain orientation of Glu275 alters the topology of the triglycerol pocket, which accommodates an additional lipophilic substitution at the benzene ring and may provide an explanation for the increased activity of BANA 207 against Influenza B virus NA.
A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase.,Lommer BS, Ali SM, Bajpai SN, Brouillette WJ, Air GM, Luo M Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1017-23. Epub 2004, May 21. PMID:15159560[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lommer BS, Ali SM, Bajpai SN, Brouillette WJ, Air GM, Luo M. A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase. Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1017-23. Epub 2004, May 21. PMID:15159560 doi:10.1107/S0907444904006225
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