View source for 6vbh


==Human XPG endonuclease catalytic domain==
<StructureSection load='6vbh' size='340' side='right'caption='[[6vbh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vbh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Pyrococcus_furiosus Pyrococcus furiosus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VBH 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]] 1.995&#8491;</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=6vbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vbh OCA], [https://pdbe.org/6vbh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vbh RCSB], [https://www.ebi.ac.uk/pdbsum/6vbh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vbh ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ERCC5_HUMAN ERCC5_HUMAN] Xeroderma pigmentosum complementation group G;COFS syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/ERCC5_HUMAN ERCC5_HUMAN] Single-stranded structure-specific DNA endonuclease involved in DNA excision repair. Makes the 3'incision in DNA nucleotide excision repair (NER). Acts as a cofactor for a DNA glycosylase that removes oxidized pyrimidines from DNA. May also be involved in transcription-coupled repair of this kind of damage, in transcription by RNA polymerase II, and perhaps in other processes too.[https://www.uniprot.org/uniprot/FEN_PYRFU FEN_PYRFU] Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Binds the unpaired 3'-DNA end and kinks the DNA to facilitate 5' cleavage specificity. Cleaves one nucleotide into the double-stranded DNA from the junction in flap DNA, leaving a nick for ligation. Also involved in the base excision repair (BER) pathway. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA.<ref>PMID:10486005</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Xeroderma pigmentosum group G (XPG) protein is both a functional partner in multiple DNA damage responses (DDR) and a pathway coordinator and structure-specific endonuclease in nucleotide excision repair (NER). Different mutations in the XPG gene ERCC5 lead to either of two distinct human diseases: Cancer-prone xeroderma pigmentosum (XP-G) or the fatal neurodevelopmental disorder Cockayne syndrome (XP-G/CS). To address the enigmatic structural mechanism for these differing disease phenotypes and for XPG's role in multiple DDRs, here we determined the crystal structure of human XPG catalytic domain (XPGcat), revealing XPG-specific features for its activities and regulation. Furthermore, XPG DNA binding elements conserved with FEN1 superfamily members enable insights on DNA interactions. Notably, all but one of the known pathogenic point mutations map to XPGcat, and both XP-G and XP-G/CS mutations destabilize XPG and reduce its cellular protein levels. Mapping the distinct mutation classes provides structure-based predictions for disease phenotypes: Residues mutated in XP-G are positioned to reduce local stability and NER activity, whereas residues mutated in XP-G/CS have implied long-range structural defects that would likely disrupt stability of the whole protein, and thus interfere with its functional interactions. Combined data from crystallography, biochemistry, small angle X-ray scattering, and electron microscopy unveil an XPG homodimer that binds, unstacks, and sculpts duplex DNA at internal unpaired regions (bubbles) into strongly bent structures, and suggest how XPG complexes may bind both NER bubble junctions and replication forks. Collective results support XPG scaffolding and DNA sculpting functions in multiple DDR processes to maintain genome stability.

Human XPG nuclease structure, assembly, and activities with insights for neurodegeneration and cancer from pathogenic mutations.,Tsutakawa SE, Sarker AH, Ng C, Arvai AS, Shin DS, Shih B, Jiang S, Thwin AC, Tsai MS, Willcox A, Her MZ, Trego KS, Raetz AG, Rosenberg D, Bacolla A, Hammel M, Griffith JD, Cooper PK, Tainer JA Proc Natl Acad Sci U S A. 2020 Jun 10. pii: 1921311117. doi:, 10.1073/pnas.1921311117. PMID:32522879<ref>PMID:32522879</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vbh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Pyrococcus furiosus]]
[[Category: Arvai AS]]
[[Category: Tainer JA]]
[[Category: Tsutakawa SE]]