Structure and function of the multifunctional DNA-repair enzyme exonuclease III (original) (raw)
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- Published: 23 March 1995
Nature volume 374, pages 381–386 (1995)Cite this article
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Abstract
THE repair of DNA requires the removal of abasic sites, which are constantly generated in vivo both spontaneously1 and by enzymatic removal of uracil2, and of bases damaged by active oxygen species, alkylating agents and ionizing radiation3,4. The major apurinic/ apyrimidinic (AP) DNA-repair endonuclease in Escherichia coli is the multifunctional enzyme exonuclease III, which also exhibits 3′-repair diesterase, 3′→ 5′ exonuclease, 3′-phosphomonoesterase and ribonuclease activities5. We report here the 1.7 Å resolution crystal structure of exonuclease III which reveals a 2-fold symmetric, four-layered ap fold with similarities to both deoxyribo-nuclease I6 and RNase H7. In the ternary complex determined at 2.6 Å resolution, Mn2+ and dCMP bind to exonuclease III at one end of the αβ-sandwich, in a region dominated by positive electrostatic potential. Residues conserved among AP endonucleases from bacteria to man cluster within this active site and appear to participate in phosphate-bond cleavage at AP sites through a nucleophilic attack facilitated by a single bound metal ion.
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Author notes
- Che-Fu Kuo
Present address: Department of Structural Biology, Department 46Y, Building AP9A, Abbott Laboratories, One Abbott Park Road, Abbott Park, Illinois, 60064, USA
Authors and Affiliations
- Department of Molecular Biology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California, 92037, USA
Clifford D. Mol, Che-Fu Kuo, Maria M. Thayer & John A. Tainer - Department of Biological Sciences, Center for Biochemistry and Biophysics, State University of New York-Albany, Albany, New York, 12222, USA
Richard P. Cunningham
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- Clifford D. Mol
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Mol, C., Kuo, CF., Thayer, M. et al. Structure and function of the multifunctional DNA-repair enzyme exonuclease III.Nature 374, 381–386 (1995). https://doi.org/10.1038/374381a0
- Received: 09 November 1994
- Accepted: 26 January 1995
- Issue Date: 23 March 1995
- DOI: https://doi.org/10.1038/374381a0