2FBV
WRN exonuclease, Mn complex
Summary for 2FBV
Entry DOI | 10.2210/pdb2fbv/pdb |
Related | 2FBT 2FBX 2FBY 2FC0 |
Descriptor | Werner syndrome helicase, MANGANESE (II) ION (3 entities in total) |
Functional Keywords | recq, wrn, werner syndrome, 3'-5' exonuclease, dnaq family, transferase |
Biological source | Homo sapiens (human) |
Cellular location | Nucleus, nucleolus: Q14191 |
Total number of polymer chains | 1 |
Total formula weight | 23540.74 |
Authors | Perry, J.J. (deposition date: 2005-12-10, release date: 2006-04-25, Last modification date: 2023-08-30) |
Primary citation | Perry, J.J.,Yannone, S.M.,Holden, L.G.,Hitomi, C.,Asaithamby, A.,Han, S.,Cooper, P.K.,Chen, D.J.,Tainer, J.A. WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing. Nat.Struct.Mol.Biol., 13:414-422, 2006 Cited by PubMed Abstract: 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. PubMed: 16622405DOI: 10.1038/nsmb1088 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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