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4p1u

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Revision as of 12:56, 5 August 2016

Influenza A (flu) virus polymerase basic protein 2 (PB2) bound to VX787, an azaindole inhibitor

Structural highlights

4p1u is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PB2_I75A3] Involved in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNA are used to generate primers for viral transcription. Binds the cap of the target pre-RNA which is subsequently cleaved by PB1. May play a role in genome replication (By similarity).

Publication Abstract from PubMed

In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay ( Wagaman , P. C. , Leong , M. A. , and Simmen , K. A. Development of a novel influenza A antiviral assay . J. Virol. Methods 2002 , 105 , 105 - 114 ) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.

Discovery of a Novel, First-in-Class, Orally Bioavailable Azaindole Inhibitor (VX-787) of Influenza PB2.,Clark MP, Ledeboer MW, Davies I, Byrn RA, Jones SM, Perola E, Tsai A, Jacobs M, Nti-Addae K, Bandarage UK, Boyd MJ, Bethiel RS, Court JJ, Deng H, Duffy JP, Dorsch WA, Farmer LJ, Gao H, Gu W, Jackson K, Jacobs DH, Kennedy JM, Ledford B, Liang J, Maltais F, Murcko M, Wang T, Wannamaker MW, Bennett HB, Leeman JR, McNeil C, Taylor WP, Memmott C, Jiang M, Rijnbrand R, Bral C, Germann U, Nezami A, Zhang Y, Salituro FG, Bennani YL, Charifson PS J Med Chem. 2014 Jul 24. PMID:25019388^[1]

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

References

↑ Clark MP, Ledeboer MW, Davies I, Byrn RA, Jones SM, Perola E, Tsai A, Jacobs M, Nti-Addae K, Bandarage UK, Boyd MJ, Bethiel RS, Court JJ, Deng H, Duffy JP, Dorsch WA, Farmer LJ, Gao H, Gu W, Jackson K, Jacobs DH, Kennedy JM, Ledford B, Liang J, Maltais F, Murcko M, Wang T, Wannamaker MW, Bennett HB, Leeman JR, McNeil C, Taylor WP, Memmott C, Jiang M, Rijnbrand R, Bral C, Germann U, Nezami A, Zhang Y, Salituro FG, Bennani YL, Charifson PS. Discovery of a Novel, First-in-Class, Orally Bioavailable Azaindole Inhibitor (VX-787) of Influenza PB2. J Med Chem. 2014 Jul 24. PMID:25019388 doi:http://dx.doi.org/10.1021/jm5007275

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/4p1u"

@@ Line 1: / Line 1: @@
 ==Influenza A (flu) virus polymerase basic protein 2 (PB2) bound to VX787, an azaindole inhibitor==
 <StructureSection load='4p1u' size='340' side='right' caption='[[4p1u]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4p1u]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P1U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P1U FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=21G:(2S,3S)-3-[[5-FLUORANYL-2-(5-FLUORANYL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PYRIMIDIN-4-YL]AMINO]BICYCLO[2.2.2]OCTANE-2-CARBOXYLIC+ACID'>21G</scene></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=4p1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p1u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p1u RCSB], [http://www.ebi.ac.uk/pdbsum/4p1u 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=4p1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p1u OCA], [http://pdbe.org/4p1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p1u RCSB], [http://www.ebi.ac.uk/pdbsum/4p1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p1u ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4p1u" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[RNA polymerase|RNA polymerase]]
 == References ==
 <references/>

4p1u

From Proteopedia

Revision as of 12:56, 5 August 2016

Influenza A (flu) virus polymerase basic protein 2 (PB2) bound to VX787, an azaindole inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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