3tib

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of 1957 pandemic H2N2 neuraminidase complexed with laninamivir octanoate

Structural highlights

3tib is a 4 chain structure with sequence from Influenza A virus (A/RI/5+/1957(H2N2)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.201Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q194T1_9INFA

Publication Abstract from PubMed

The 2009 H1N1 influenza pandemic (pH1N1) led to record sales of neuraminidase (NA) inhibitors, which has contributed significantly to the recent increase in oseltamivir-resistant viruses. Therefore, development and careful evaluation of novel NA inhibitors is of great interest. Recently, a highly potent NA inhibitor, laninamivir, has been approved for use in Japan. Laninamivir is effective using a single inhaled dose via its octanoate prodrug (CS-8958) and has been demonstrated to be effective against oseltamivir-resistant NA in vitro. However, effectiveness of laninamivir octanoate prodrug against oseltamivir-resistant influenza infection in adults has not been demonstrated. NA is classified into 2 groups based upon phylogenetic analysis and it is becoming clear that each group has some distinct structural features. Recently, we found that pH1N1 N1 NA (p09N1) is an atypical group 1 NA with some group 2-like features in its active site (lack of a 150-cavity). Furthermore, it has been reported that certain oseltamivir-resistant substitutions in the NA active site are group 1 specific. In order to comprehensively evaluate the effectiveness of laninamivir, we utilized recombinant N5 (typical group 1), p09N1 (atypical group 1) and N2 from the 1957 pandemic H2N2 (p57N2) (typical group 2) to carry out in vitro inhibition assays. We found that laninamivir and its octanoate prodrug display group specific preferences to different influenza NAs and provide the structural basis of their specific action based upon their novel complex crystal structures. Our results indicate that laninamivir and zanamivir are more effective against group 1 NA with a 150-cavity than group 2 NA with no 150-cavity. Furthermore, we have found that the laninamivir octanoate prodrug has a unique binding mode in p09N1 that is different from that of group 2 p57N2, but with some similarities to NA-oseltamivir binding, which provides additional insight into group specific differences of oseltamivir binding and resistance.

Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza na inhibition.,Vavricka CJ, Li Q, Wu Y, Qi J, Wang M, Liu Y, Gao F, Liu J, Feng E, He J, Wang J, Liu H, Jiang H, Gao GF PLoS Pathog. 2011 Oct;7(10):e1002249. Epub 2011 Oct 20. PMID:22028647^[1]

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

References

↑ Vavricka CJ, Li Q, Wu Y, Qi J, Wang M, Liu Y, Gao F, Liu J, Feng E, He J, Wang J, Liu H, Jiang H, Gao GF. Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza na inhibition. PLoS Pathog. 2011 Oct;7(10):e1002249. Epub 2011 Oct 20. PMID:22028647 doi:10.1371/journal.ppat.1002249

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/3tib"

@@ Line 3: / Line 3: @@
 <StructureSection load='3tib' size='340' side='right'caption='[[3tib]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3tib]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_a_virus_(a/ri/5+/1957(h2n2)) Influenza a virus (a/ri/5+/1957(h2n2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TIB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TIB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3tib]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/RI/5+/1957(H2N2)) Influenza A virus (A/RI/5+/1957(H2N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TIB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TIB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=LVO:5-(ACETYLAMINO)-2,6-ANHYDRO-4-CARBAMIMIDAMIDO-3,4,5-TRIDEOXY-7-O-METHYL-9-O-OCTANOYL-D-GLYCERO-D-GALACTO-NON-2-ENONIC+ACID'>LVO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.201&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ti3|3ti3]], [[3ti4|3ti4]], [[3ti5|3ti5]], [[3ti6|3ti6]], [[3ti8|3ti8]], [[3tia|3tia]], [[3tic|3tic]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=LVO:5-(ACETYLAMINO)-2,6-ANHYDRO-4-CARBAMIMIDAMIDO-3,4,5-TRIDEOXY-7-O-METHYL-9-O-OCTANOYL-D-GLYCERO-D-GALACTO-NON-2-ENONIC+ACID'>LVO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=3tib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tib OCA], [https://pdbe.org/3tib PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tib RCSB], [https://www.ebi.ac.uk/pdbsum/3tib PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tib ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q194T1_9INFA Q194T1_9INFA]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Feng, E]]
+[[Category: Feng E]]
-[[Category: Gao, F]]
+[[Category: Gao F]]
-[[Category: Gao, G F]]
+[[Category: Gao GF]]
-[[Category: He, J]]
+[[Category: He J]]
-[[Category: Jiang, H]]
+[[Category: Jiang H]]
-[[Category: Li, Q]]
+[[Category: Li Q]]
-[[Category: Liu, H]]
+[[Category: Liu H]]
-[[Category: Liu, J]]
+[[Category: Liu J]]
-[[Category: Liu, Y]]
+[[Category: Liu Y]]
-[[Category: Qi, J]]
+[[Category: Qi J]]
-[[Category: Vavricka, C J]]
+[[Category: Vavricka CJ]]
-[[Category: Wang, J]]
+[[Category: Wang J]]
-[[Category: Wang, M]]
+[[Category: Wang M]]
-[[Category: Wu, Y]]
+[[Category: Wu Y]]
-[[Category: 6-bladed beta-propeller]]
-[[Category: Antiviral]]
-[[Category: Calcium binding]]
-[[Category: Glycosylation]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]

3tib

From Proteopedia

Current revision

Crystal structure of 1957 pandemic H2N2 neuraminidase complexed with laninamivir octanoate

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox