7rds
From Proteopedia
(Difference between revisions)
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==Structure of human NTHL1== | ==Structure of human NTHL1== | ||
| - | <StructureSection load='7rds' size='340' side='right'caption='[[7rds]]' scene=''> | + | <StructureSection load='7rds' size='340' side='right'caption='[[7rds]], [[Resolution|resolution]] 2.50Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RDS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7rds]] 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=7RDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RDS FirstGlance]. <br> |
| - | </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=7rds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rds OCA], [https://pdbe.org/7rds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rds RCSB], [https://www.ebi.ac.uk/pdbsum/7rds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rds ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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=7rds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rds OCA], [https://pdbe.org/7rds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rds RCSB], [https://www.ebi.ac.uk/pdbsum/7rds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rds ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/NTH_HUMAN NTH_HUMAN] NTHL1-related attenuated familial adenomatous polyposis. The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NTH_HUMAN NTH_HUMAN] Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage (PubMed:9927729). The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP-lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines. Has also 8-oxo-7,8-dihydroguanine (8-oxoG) DNA glycosylase activity. Acts preferentially on DNA damage opposite guanine residues in DNA. Is able to process lesions in nucleosomes without requiring or inducing nucleosome disruption.[HAMAP-Rule:MF_03183]<ref>PMID:10882850</ref> <ref>PMID:11328882</ref> <ref>PMID:11380260</ref> <ref>PMID:11695910</ref> <ref>PMID:12140329</ref> <ref>PMID:12144783</ref> <ref>PMID:12519758</ref> <ref>PMID:14734554</ref> <ref>PMID:15533839</ref> <ref>PMID:17923696</ref> <ref>PMID:20005182</ref> <ref>PMID:20110254</ref> <ref>PMID:21930793</ref> <ref>PMID:8990169</ref> <ref>PMID:9045706</ref> <ref>PMID:9705289</ref> <ref>PMID:9890904</ref> <ref>PMID:9927729</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Base excision repair (BER) is the main pathway protecting cells from the continuous damage to DNA inflicted by reactive oxygen species. BER is initiated by DNA glycosylases, each of which repairs a particular class of base damage. NTHL1, a bifunctional DNA glycosylase, possesses both glycolytic and beta-lytic activities with a preference for oxidized pyrimidine substrates. Defects in human NTHL1 drive a class of polyposis colorectal cancer. We report the first X-ray crystal structure of hNTHL1, revealing an open conformation not previously observed in the bacterial orthologs. In this conformation, the six-helical barrel domain comprising the helix-hairpin-helix (HhH) DNA binding motif is tipped away from the iron sulphur cluster-containing domain, requiring a conformational change to assemble a catalytic site upon DNA binding. We found that the flexibility of hNTHL1 and its ability to adopt an open configuration can be attributed to an interdomain linker. Swapping the human linker sequence for that of Escherichia coli yielded a protein chimera that crystallized in a closed conformation and had a reduced activity on lesion-containing DNA. This large scale interdomain rearrangement during catalysis is unprecedented for a HhH superfamily DNA glycosylase and provides important insight into the molecular mechanism of hNTHL1. | ||
| + | |||
| + | Caught in motion: human NTHL1 undergoes interdomain rearrangement necessary for catalysis.,Carroll BL, Zahn KE, Hanley JP, Wallace SS, Dragon JA, Doublie S Nucleic Acids Res. 2021 Dec 16;49(22):13165-13178. doi: 10.1093/nar/gkab1162. PMID:34871433<ref>PMID:34871433</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7rds" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Carroll BL]] | [[Category: Carroll BL]] | ||
[[Category: Doublie S]] | [[Category: Doublie S]] | ||
[[Category: Zahn KE]] | [[Category: Zahn KE]] | ||
Current revision
Structure of human NTHL1
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