6evj

<StructureSection load='6evj' size='340' side='right' caption='[[6evj]], [[Resolution|resolution]] 3.90&Aring;' scene=''>

<table><tr><td colspan='2'>[[6evj]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EVJ FirstGlance]. <br>

</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8NK:7-METHYLGUANOSINE+5-DIPHOSPHATE'>8NK</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=6evj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6evj OCA], [http://pdbe.org/6evj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6evj RCSB], [http://www.ebi.ac.uk/pdbsum/6evj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6evj ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

Influenza polymerase uses short capped primers snatched from nascent Pol II transcripts to initiate transcription of viral mRNAs. Here we describe crystal structures of influenza A and B polymerase bound to a capped primer in a configuration consistent with transcription initiation ('priming state') and show by functional assays that conserved residues from both the PB2 midlink and cap-binding domains are important for positioning the capped RNA. In particular, mutation of PB2 Arg264, which interacts with the triphosphate linkage in the cap, significantly and specifically decreases cap-dependent transcription. We also compare the configuration of the midlink and cap-binding domains in the priming state with their very different relative arrangement (called the 'apo' state) in structures where the potent cap-binding inhibitor VX-787, or a close analogue, is bound. In the 'apo' state the inhibitor makes additional interactions to the midlink domain that increases its affinity beyond that to the cap-binding domain alone. The comparison suggests that the mechanism of resistance of certain mutations that allow virus to escape from VX-787, notably PB2 N510T, can only be rationalized if VX-787 has a dual mode of action, direct inhibition of capped RNA binding as well as stabilization of the transcriptionally inactive 'apo' state.

 

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== References ==

[[Category: RNA-directed RNA polymerase]]

[[Category: Pflug, A]]

[[Category: Capped rna primer]]

[[Category: Influenza virus]]

[[Category: Rna-dependent rna polymerase]]

[[Category: Viral protein]]