6s5v

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the Cap-Midlink region of the H5N1 Influenza A virus polymerase in complex with a Cap-domain binding analogue

Structural highlights

6s5v is a 2 chain structure with sequence from Influenza a virus (a/duck/fujian/13/2002(h5n1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	PB2 (Influenza A virus (A/duck/Fujian/13/2002(H5N1)))
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[Q6E3N3_9INFA] Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex.[HAMAP-Rule:MF_04062][SAAS:SAAS01041023]

Publication Abstract from PubMed

In the search for novel influenza inhibitors we evaluated 7-fluoro-substituted indoles as bioisosteric replacements for the 7-azaindole scaffold of Pimodivir, a PB2 (polymerase basic protein 2) inhibitor currently in clinical development. Specifically, a 5,7-difluoroindole derivative 11a was identified as a potent and metabolically stable influenza inhibitor. 11a demonstrated a favorable oral pharmacokinetic profile and in vivo efficacy in mice. In addition, it was found that 11a was not at risk of metabolism via aldehyde oxidase, an advantage over previously described inhibitors of this class. The crystal structure of 11a bound to influenza A PB2 cap region is disclosed here and deposited to the PDB.

Design, Synthesis, and Biological Evaluation of Novel Indoles Targeting the Influenza PB2 Cap Binding Region.,McGowan DC, Balemans W, Embrechts W, Motte M, Keown JR, Buyck C, Corbera J, Funes M, Moreno L, Cooymans L, Tahri A, Eymard J, Stoops B, Strijbos R, Van den Berg J, Fodor E, Grimes JM, Koul A, Jonckers THM, Raboisson P, Guillemont J J Med Chem. 2019 Oct 30. doi: 10.1021/acs.jmedchem.9b01091. PMID:31647875^[1]

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

References

↑ McGowan DC, Balemans W, Embrechts W, Motte M, Keown JR, Buyck C, Corbera J, Funes M, Moreno L, Cooymans L, Tahri A, Eymard J, Stoops B, Strijbos R, Van den Berg J, Fodor E, Grimes JM, Koul A, Jonckers THM, Raboisson P, Guillemont J. Design, Synthesis, and Biological Evaluation of Novel Indoles Targeting the Influenza PB2 Cap Binding Region. J Med Chem. 2019 Oct 30. doi: 10.1021/acs.jmedchem.9b01091. PMID:31647875 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01091

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6s5v"

@@ Line 3: / Line 3: @@
 <StructureSection load='6s5v' size='340' side='right'caption='[[6s5v]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6s5v]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S5V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6s5v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/duck/fujian/13/2002(h5n1)) Influenza a virus (a/duck/fujian/13/2002(h5n1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S5V FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=KWN:(1~{S},2~{S},3~{S},6~{R})-2-[[2-[5,7-bis(fluoranyl)-1~{H}-indol-3-yl]-5-fluoranyl-pyrimidin-4-yl]amino]-3,6-dimethyl-cyclohexane-1-carboxylic+acid'>KWN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=274828 Influenza A virus (A/duck/Fujian/13/2002(H5N1))])</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=6s5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s5v OCA], [http://pdbe.org/6s5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s5v RCSB], [http://www.ebi.ac.uk/pdbsum/6s5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s5v ProSAT]</span></td></tr>
 </table>

6s5v

From Proteopedia

Current revision

Crystal structure of the Cap-Midlink region of the H5N1 Influenza A virus polymerase in complex with a Cap-domain binding analogue

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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