Structure of the endonuclease IV homologue from Thermotoga maritima in the presence of active-site divalent metal ions.
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.
Tomanicek
Stephen J
SJ
Oak Ridge National Laboratory, Neutron Scattering Science Division, 1 Bethel Valley Road, Oak Ridge, TN 37831, USA.
Hughes
Ronny C
RC
Ng
Joseph D
JD
Coates
Leighton
L
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
D002413:Cations, Divalent; D043223:Deoxyribonuclease IV (Phage T4-Induced); D015032:Zinc
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