2fc0: Difference between revisions
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|PDB= 2fc0 |SIZE=350|CAPTION= <scene name='initialview01'>2fc0</scene>, resolution 2.00Å | |PDB= 2fc0 |SIZE=350|CAPTION= <scene name='initialview01'>2fc0</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=DGP:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DGP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= WRN, RECQ3, RECQL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= WRN, RECQ3, RECQL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2fbt|2FBT]], [[2fbv|2FBV]], [[2fbx|2FBX]], [[2fc0|2FC0]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fc0 OCA], [http://www.ebi.ac.uk/pdbsum/2fc0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fc0 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
WRN is unique among the five human RecQ DNA helicases in having a functional exonuclease domain (WRN-exo) and being defective in the premature aging and cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal structures, biochemical activity and participation in DNA end joining. Metal-ion complex structures, active site mutations and activity assays reveal a nuclease mechanism mediated by two metal ions. The DNA end-binding Ku70/80 complex specifically stimulates WRN-exo activity, and structure-based mutational inactivation of WRN-exo alters DNA end joining in human cells. We furthermore establish structural and biochemical similarities of WRN-exo to DnaQ-family replicative proofreading exonucleases, describing WRN-specific adaptations consistent with double-stranded DNA specificity and functionally important conformational changes. These results indicate WRN-exo is a human DnaQ family member and support DnaQ-like proofreading activities stimulated by Ku70/80, with implications for WRN functions in age-related pathologies and maintenance of genomic integrity. | WRN is unique among the five human RecQ DNA helicases in having a functional exonuclease domain (WRN-exo) and being defective in the premature aging and cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal structures, biochemical activity and participation in DNA end joining. Metal-ion complex structures, active site mutations and activity assays reveal a nuclease mechanism mediated by two metal ions. The DNA end-binding Ku70/80 complex specifically stimulates WRN-exo activity, and structure-based mutational inactivation of WRN-exo alters DNA end joining in human cells. We furthermore establish structural and biochemical similarities of WRN-exo to DnaQ-family replicative proofreading exonucleases, describing WRN-specific adaptations consistent with double-stranded DNA specificity and functionally important conformational changes. These results indicate WRN-exo is a human DnaQ family member and support DnaQ-like proofreading activities stimulated by Ku70/80, with implications for WRN functions in age-related pathologies and maintenance of genomic integrity. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Perry, J J.]] | [[Category: Perry, J J.]] | ||
[[Category: Tainer, J A.]] | [[Category: Tainer, J A.]] | ||
[[Category: 3'-5' exonuclease]] | [[Category: 3'-5' exonuclease]] | ||
[[Category: dnaq family]] | [[Category: dnaq family]] | ||
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[[Category: wrn]] | [[Category: wrn]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:00:42 2008'' | ||
