title: Structure of the endonuclease IV homologue from Thermotoga maritima in the presence of active-site divalent metal ions.
abstract: The most frequent lesion in DNA is at apurinic/apyrimidinic (AP) sites resulting from DNA-base losses. These AP-site lesions can stall DNA replication and lead to genome instability if left unrepaired. The AP endonucleases are an important class of enzymes that are involved in the repair of AP-site intermediates during damage-general DNA base-excision repair pathways. These enzymes hydrolytically cleave the 5'-phosphodiester bond at an AP site to generate a free 3'-hydroxyl group and a 5'-terminal sugar phosphate using their AP nuclease activity. Specifically, Thermotoga maritima endonuclease IV is a member of the second conserved AP endonuclease family that includes Escherichia coli endonuclease IV, which is the archetype of the AP endonuclease superfamily. In order to more fully characterize the AP endonuclease family of enzymes, two X-ray crystal structures of the T. maritima endonuclease IV homologue were determined in the presence of divalent metal ions bound in the active-site region. These structures of the T. maritima endonuclease IV homologue further revealed the use of the TIM-barrel fold and the trinuclear metal binding site as important highly conserved structural elements that are involved in DNA-binding and AP-site repair processes in the AP endonuclease superfamily.
authors.affiliation: Oak Ridge National Laboratory, Neutron Scattering Science Division, 1 Bethel Valley Road, Oak Ridge, TN 37831, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tomanicek
authors.forename: Ronny C
authors.initials: RC
authors.lastname: Hughes
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Ng
authors.forename: Leighton
authors.initials: L
authors.lastname: Coates
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D002413:Cations, Divalent / Q000737:chemistry; D018360:Crystallography, X-Ray; D043223:Deoxyribonuclease IV (Phage T4-Induced) / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D020124:Thermotoga maritima / Q000201:enzymology*; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D043223:Deoxyribonuclease IV (Phage T4-Induced); D015032:Zinc
references.citation: J Bacteriol. 1999 May;181(9):2834-9
references.pmid: 10217775
references.citation: Nucleic Acids Res. 1999 Mar 1;27(5):1223-42
references.pmid: 9973609
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: Annu Rev Genet. 1986;20:201-30
references.pmid: 3545059
references.citation: DNA Repair (Amst). 2007 Apr 1;6(4):410-28
references.pmid: 17208522
references.citation: Mutat Res. 1990 Sep-Nov;236(2-3):173-201
references.pmid: 1697933
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Prog Nucleic Acid Res Mol Biol. 1985;32:115-54
references.pmid: 3003798
references.citation: J Biol Chem. 1988 Jun 15;263(17):8066-71
references.pmid: 2453510
references.citation: Nat Struct Mol Biol. 2008 May;15(5):515-22
references.pmid: 18408731
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2564-9
references.pmid: 16473948
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2256-68
references.pmid: 15572779
references.citation: BMC Biotechnol. 2008 Apr 29;8:44
references.pmid: 18445293
references.citation: Curr Opin Genet Dev. 1997 Apr;7(2):158-69
references.pmid: 9115419
references.citation: Mutat Res. 1997 May 1;383(3):189-96
references.pmid: 9164479
references.citation: Nucleic Acids Res. 1990 Sep 11;18(17):5069-75
references.pmid: 1698278
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
references.pmid: 20057044
references.citation: Nature. 1975 Jun 19;255(5510):609-14
references.pmid: 1134550
references.citation: Mutat Res. 2005 Sep 4;577(1-2):55-76
references.pmid: 15941573
references.citation: Bioessays. 1995 Aug;17(8):713-9
references.pmid: 7661852
references.citation: Mol Cell Biol. 2005 Aug;25(15):6380-90
references.pmid: 16024777
references.citation: J Biol Chem. 2003 Oct 10;278(41):39951-9
references.pmid: 12882965
references.citation: Nucleic Acids Res. 1989 May 11;17(9):3617-8
references.pmid: 2471157
references.citation: Biochemistry. 1999 Mar 23;38(12):3615-23
references.pmid: 10090748
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
references.pmid: 12393927
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Dec 1;65(Pt 12):1317-9
references.pmid: 20054139
references.citation: Nucleic Acids Res. 2003 Nov 1;31(21):6344-53
references.pmid: 14576322
references.citation: Proc Natl Acad Sci U S A. 1986 Oct;83(20):7731-5
references.pmid: 2429316
references.citation: Mutat Res. 2000 Aug 30;460(3-4):211-29
references.pmid: 10946230
references.citation: Cell. 1999 Aug 6;98(3):397-408
references.pmid: 10458614
references.citation: Nature. 2002 Jan 10;415(6868):183-7
references.pmid: 11805838
references.citation: Trends Biochem Sci. 1990 Jun;15(6):228-34
references.pmid: 2200166
references.citation: Biochem Cell Biol. 1997;75(4):327-36
references.pmid: 9493955
references.citation: FASEB J. 1995 Apr;9(7):497-503
references.pmid: 7737457
references.citation: J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
references.pmid: 19461840
references.citation: Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-4
references.pmid: 1722334
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1465-70
references.pmid: 17242363
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: Biochem J. 1997 Jul 1;325 ( Pt 1):1-16
references.pmid: 9224623
references.citation: J Biol Chem. 2003 Jan 31;278(5):3048-54
references.pmid: 12444080
references.citation: Nat Genet. 2003 Jul;34(3):239-41
references.pmid: 12833042