2fbv
From Proteopedia
(New page: 200px<br /> <applet load="2fbv" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fbv, resolution 2.40Å" /> '''WRN exonuclease, Mn...) |
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| - | [[Image:2fbv.gif|left|200px]]<br /> | + | [[Image:2fbv.gif|left|200px]]<br /><applet load="2fbv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2fbv" size=" | + | |
caption="2fbv, resolution 2.40Å" /> | caption="2fbv, resolution 2.40Å" /> | ||
'''WRN exonuclease, Mn complex'''<br /> | '''WRN exonuclease, Mn complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | WRN is unique among the five human RecQ DNA helicases in having a | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2FBV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2FBV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MN:'>MN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FBV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Perry, J | + | [[Category: Perry, J J.]] |
[[Category: MN]] | [[Category: MN]] | ||
[[Category: 3'-5' exonuclease]] | [[Category: 3'-5' exonuclease]] | ||
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[[Category: wrn]] | [[Category: wrn]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:19:45 2008'' |
Revision as of 15:19, 21 February 2008
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WRN exonuclease, Mn complex
Contents |
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.
Disease
Known diseases associated with this structure: Werner syndrome OMIM:[604611]
About this Structure
2FBV is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing., Perry JJ, Yannone SM, Holden LG, Hitomi C, Asaithamby A, Han S, Cooper PK, Chen DJ, Tainer JA, Nat Struct Mol Biol. 2006 May;13(5):414-22. Epub 2006 Apr 23. PMID:16622405
Page seeded by OCA on Thu Feb 21 17:19:45 2008
Categories: Homo sapiens | Single protein | Perry, J J. | MN | 3'-5' exonuclease | Dnaq family | Recq | Werner syndrome | Wrn
