2brf
From Proteopedia
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| - | [[Image:2brf.gif|left|200px]]<br /><applet load="2brf" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2brf, resolution 1.40Å" /> | ||
| - | '''CRYSTAL STRUCTURE OF THE FHA DOMAIN OF HUMAN POLYNUCLEOTIDE KINASE 3' PHOSPHATASE'''<br /> | ||
| - | == | + | ==Crystal Structure of the FHA Domain of Human Polynucleotide Kinase 3' Phosphatase== |
| - | + | <StructureSection load='2brf' size='340' side='right'caption='[[2brf]], [[Resolution|resolution]] 1.40Å' scene=''> | |
| - | [ | + | == Structural highlights == |
| - | [ | + | <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> |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4Å</td></tr> | |
| - | + | <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> | |
| - | [ | + | <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. | ||
| - | + | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2brf" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ali AAE]] | ||
| + | [[Category: Oliver AW]] | ||
| + | [[Category: Pearl LH]] | ||
Current revision
Crystal Structure of the FHA Domain of Human Polynucleotide Kinase 3' Phosphatase
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