1iny

From Proteopedia

(Difference between revisions)

Revision as of 09:12, 10 January 2018

A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES

Structural highlights

1iny is a 1 chain structure with sequence from 9infa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by ePANA was approximately a 100-fold better than by sialic acid, but inhibition of type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound was not a strong inhibitor for any of the NA strains tested. The crystal structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9) NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of the PANA compounds distorted the NA active site upon binding. No significant differences in the NA-ePANA complex structures were found to explain the anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis that an increase in the ePANA inhibition compared to that caused by sialic acid is due to (1) a stronger electrostatic interaction between the inhibitor phosphonyl group and the active site arginine pocket and (2) a lower distortion energy requirement for binding of ePANA.

A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.,White CL, Janakiraman MN, Laver WG, Philippon C, Vasella A, Air GM, Luo M J Mol Biol. 1995 Feb 3;245(5):623-34. PMID:7844831^[1]

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

References

↑ White CL, Janakiraman MN, Laver WG, Philippon C, Vasella A, Air GM, Luo M. A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies. J Mol Biol. 1995 Feb 3;245(5):623-34. PMID:7844831

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1iny"

@@ Line 1: / Line 1: @@
 ==A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES==
 <StructureSection load='1iny' size='340' side='right' caption='[[1iny]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1iny]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/9infa 9infa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1INY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1INY 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=EQP:(4-ACETAMIDO-2,4-DIDEOXY-D-GLYCERO-ALPHA-D-GALACTO-1-OCTOPYRANOSYL)PHOSPHONIC+ACID'>EQP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=EQP:(4-ACETAMIDO-2,4-DIDEOXY-D-GLYCERO-ALPHA-D-GALACTO-1-OCTOPYRANOSYL)PHOSPHONIC+ACID'>EQP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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='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=1iny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iny OCA], [http://pdbe.org/1iny PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1iny RCSB], [http://www.ebi.ac.uk/pdbsum/1iny PDBsum]</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=1iny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iny OCA], [http://pdbe.org/1iny PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1iny RCSB], [http://www.ebi.ac.uk/pdbsum/1iny PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1iny ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/in/1iny_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/in/1iny_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 28: / Line 29: @@
 </div>
 <div class="pdbe-citations 1iny" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Neuraminidase|Neuraminidase]]
 == References ==
 <references/>

1iny

From Proteopedia

Revision as of 09:12, 10 January 2018

A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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