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2brf

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Revision as of 06:51, 16 May 2018

Crystal Structure of the FHA Domain of Human Polynucleotide Kinase 3' Phosphatase

Structural highlights

2brf is a 1 chain structure with sequence from Human. 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

Disease

[PNKP_HUMAN] Defects in PNKP are the cause of epileptic encephalopathy, early infantile, type 10 (EIEE10) [MIM: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.^[1]

Function

[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.^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[3]

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

References

↑ Shen J, Gilmore EC, Marshall CA, Haddadin M, Reynolds JJ, Eyaid W, Bodell A, Barry B, Gleason D, Allen K, Ganesh VS, Chang BS, Grix A, Hill RS, Topcu M, Caldecott KW, Barkovich AJ, Walsh CA. Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nat Genet. 2010 Mar;42(3):245-9. doi: 10.1038/ng.526. Epub 2010 Jan 31. PMID:20118933 doi:10.1038/ng.526
↑ Jilani A, Ramotar D, Slack C, Ong C, Yang XM, Scherer SW, Lasko DD. Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3'-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage. J Biol Chem. 1999 Aug 20;274(34):24176-86. PMID:10446192
↑ Ali AA, Jukes RM, Pearl LH, Oliver AW. Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK. Nucleic Acids Res. 2009 Jan 20. PMID:19155274 doi:gkn1086

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2brf"

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF THE FHA DOMAIN OF HUMAN POLYNUCLEOTIDE KINASE 3' PHOSPHATASE==
+==Crystal Structure of the FHA Domain of Human Polynucleotide Kinase 3' Phosphatase==
 <StructureSection load='2brf' size='340' side='right' caption='[[2brf]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2brf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BRF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2brf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2brf OCA], [http://pdbe.org/2brf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2brf RCSB], [http://www.ebi.ac.uk/pdbsum/2brf 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=2brf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2brf OCA], [http://pdbe.org/2brf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2brf RCSB], [http://www.ebi.ac.uk/pdbsum/2brf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2brf ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/br/2brf_consurf.spt"</scriptWhenChecked>
+    <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>

2brf

From Proteopedia

Revision as of 06:51, 16 May 2018

Crystal Structure of the FHA Domain of Human Polynucleotide Kinase 3' Phosphatase

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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