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3w09

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Revision as of 09:30, 21 February 2019

Influenza virus neuraminidase subtype N9 (TERN) complexed with 2,3-dif guanidino-neu5ac2en inhibitor

Structural highlights

3w09 is a 1 chain structure with sequence from Influenza a virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Related:	1nnc, 7nn9
Activity:	Exo-alpha-sialidase, with EC number 3.2.1.18
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

Publication Abstract from PubMed

Influenza antiviral agents play important roles in modulating disease severity and in controlling pandemics while vaccines are prepared, but the development of resistance to agents like the commonly used neuraminidase inhibitor oseltamivir may limit their future utility. We report here on a new class of specific, mechanism-based anti-influenza drugs that function through the formation of a stabilized covalent intermediate in the influenza neuraminidase enzyme, and we confirm this mode of action with structural and mechanistic studies. These compounds function in cell-based assays and in animal models, with efficacies comparable to that of the neuraminidase inhibitor zanamivir and with broad-spectrum activity against drug-resistant strains in vitro. The similarity of their structure to that of the natural substrate and their mechanism-based design make these attractive antiviral candidates.

Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity.,Kim JH, Resende R, Wennekes T, Chen HM, Bance N, Buchini S, Watts AG, Pilling P, Streltsov VA, Petric M, Liggins R, Barrett S, McKimm-Breschkin JL, Niikura M, Withers SG Science. 2013 Apr 5;340(6128):71-5. doi: 10.1126/science.1232552. Epub 2013 Feb, 21. PMID:23429702^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kim JH, Resende R, Wennekes T, Chen HM, Bance N, Buchini S, Watts AG, Pilling P, Streltsov VA, Petric M, Liggins R, Barrett S, McKimm-Breschkin JL, Niikura M, Withers SG. Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity. Science. 2013 Apr 5;340(6128):71-5. doi: 10.1126/science.1232552. Epub 2013 Feb, 21. PMID:23429702 doi:http://dx.doi.org/10.1126/science.1232552

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3w09"

@@ Line 3: / Line 3: @@
 <StructureSection load='3w09' size='340' side='right' caption='[[3w09]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3w09]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/I75a5 I75a5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W09 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W09 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3w09]] is a 1 chain structure with sequence from [http://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=3W09 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W09 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZGE:(2R,3R,4R)-3-ACETAMIDO-4-CARBAMIMIDAMIDO-5-FLUORANYL-2-[(1R,2R)-1,2,3-TRIS(OXIDANYL)PROPYL]-3,4-DIHYDRO-2H-PYRAN-6-CARBOXYLIC+ACID'>ZGE</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=ZGE:(2R,3R,4R)-3-ACETAMIDO-4-CARBAMIMIDAMIDO-5-FLUORANYL-2-[(1R,2R)-1,2,3-TRIS(OXIDANYL)PROPYL]-3,4-DIHYDRO-2H-PYRAN-6-CARBOXYLIC+ACID'>ZGE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nnc|1nnc]], [[7nn9|7nn9]]</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>
@@ Line 28: / Line 28: @@
 </StructureSection>
 [[Category: Exo-alpha-sialidase]]
-[[Category: I75a5]]
+[[Category: Influenza a virus]]
 [[Category: Streltsov, V A]]
 [[Category: Hydrolase-hydrolase inhibitor complex]]
 [[Category: Neuraminidase]]
 [[Category: Sialidase]]

3w09

From Proteopedia

Revision as of 09:30, 21 February 2019

Influenza virus neuraminidase subtype N9 (TERN) complexed with 2,3-dif guanidino-neu5ac2en inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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