2brf: Difference between revisions

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{{Seed}}
[[Image:2brf.png|left|200px]]


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==Crystal Structure of the FHA Domain of Human Polynucleotide Kinase 3' Phosphatase==
The line below this paragraph, containing "STRUCTURE_2brf", creates the "Structure Box" on the page.
<StructureSection load='2brf' size='340' side='right'caption='[[2brf]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2brf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BRF FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_2brf|  PDB=2brf  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2brf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2brf OCA], [https://pdbe.org/2brf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2brf RCSB], [https://www.ebi.ac.uk/pdbsum/2brf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2brf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PNKP_HUMAN PNKP_HUMAN] Defects in PNKP are the cause of epileptic encephalopathy, early infantile, type 10 (EIEE10) [MIM:[https://omim.org/entry/613402 613402]. A disease characterized by microcephaly, infantile-onset seizures, severe intellectual disability and delayed motor milestones with absent speech or only achieving a few words. Most patients also have behavioral problems with hyperactivity. Microcephaly is progressive and without neuronal migration or structural abnormalities, consistent with primary microcephaly.<ref>PMID:20118933</ref>
== Function ==
[https://www.uniprot.org/uniprot/PNKP_HUMAN PNKP_HUMAN] Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNK ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone.<ref>PMID:10446192</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/br/2brf_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2brf ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Short-patch repair of DNA single-strand breaks and gaps (SSB) is coordinated by XRCC1, a scaffold protein that recruits the DNA polymerase and DNA ligase required for filling and sealing the damaged strand. XRCC1 can also recruit end-processing enzymes, such as PNK (polynucleotide kinase 3'-phosphatase), Aprataxin and APLF (aprataxin/PNK-like factor), which ensure the availability of a free 3'-hydroxyl on one side of the gap, and a 5'-phosphate group on the other, for the polymerase and ligase reactions respectively. PNK binds to a phosphorylated segment of XRCC1 (between its two C-terminal BRCT domains) via its Forkhead-associated (FHA) domain. We show here, contrary to previous studies, that the FHA domain of PNK binds specifically, and with high affinity to a multiply phosphorylated motif in XRCC1 containing a pSer-pThr dipeptide, and forms a 2:1 PNK:XRCC1 complex. The high-resolution crystal structure of a PNK-FHA-XRCC1 phosphopeptide complex reveals the basis for this unusual bis-phosphopeptide recognition, which is probably a common feature of the known XRCC1-associating end-processing enzymes.


===CRYSTAL STRUCTURE OF THE FHA DOMAIN OF HUMAN POLYNUCLEOTIDE KINASE 3' PHOSPHATASE===
Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK.,Ali AA, Jukes RM, Pearl LH, Oliver AW Nucleic Acids Res. 2009 Jan 20. PMID:19155274<ref>PMID:19155274</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==About this Structure==
</div>
2BRF is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BRF OCA].
<div class="pdbe-citations 2brf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Ali, A A.E.]]
[[Category: Large Structures]]
[[Category: Oliver, A W.]]
[[Category: Ali AAE]]
[[Category: Pearl, L H.]]
[[Category: Oliver AW]]
[[Category: Ber]]
[[Category: Pearl LH]]
[[Category: Bifunctional]]
[[Category: Dna repair]]
[[Category: Dsbr]]
[[Category: Fha]]
[[Category: Forkhead-associated]]
[[Category: Pnk]]
[[Category: Pnkp]]
[[Category: Polynucleotide kinase 3' phosphatase]]
[[Category: Ssbr]]
[[Category: Transferase]]
[[Category: Xrcc1]]
[[Category: Xrcc4 hydrolase]]
 
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