InterPro domain: IPR003651

Endonuclease III ( 4.2.99.18 ) is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a beta-elimination mechanism [ 1 , 2 ]. The structurally related DNA glycosylase MutYrecognises and excises the mutational intermediate 8-oxoguanine-adenine mispair [ 3 ]. The 3-D structures of Escherichia coli endonuclease III [ 4 ] and catalytic domain of MutY [ 5 ] have been determined. Thestructures contain two all-alpha domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key,four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with theFe4S4 cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation patternCys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif isreferred to as a Fe4S4 cluster loop (FCL) [ 6 ]. Two DNA-binding motifs have been proposed, one at either end of theinterdomain groove: the helix-hairpin-helix (HhH) and FCL motifs. The primary role of the iron-sulphur cluster appears toinvolve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop ofthe FCL motif [ 7 , 7 ].

The iron-sulphur cluster loop (FCL) is also found in DNA-(apurinic or apyrimidinic site) lyase, a subfamily of endonuclease III. The enzyme has both apurinic and apyrimidinic endonuclease activity and a DNA N-glycosylase activity. It cuts damaged DNA at cytosines, thymines and guanines, and acts on the damaged strand 5' of the damaged site. The enzyme binds a 4Fe-4S cluster which is not important for the catalytic activity, but is probably involved in the alignment of the enzyme along the DNA strand.

1. DNA repair proteins. Curr. Opin. Struct. Biol. 5, 20-6
2. DNA-repair enzymes. Curr. Opin. Struct. Biol. 7, 103-9
3. The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). J. Bacteriol. 174, 6321-5
4. Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III. Science 258, 434-40
5. MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily. Nat. Struct. Biol. 5, 1058-64
6. Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure. EMBO J. 14, 4108-20
7. Positively charged residues within the iron-sulfur cluster loop of E. coli MutY participate in damage recognition and removal. Arch. Biochem. Biophys. 380, 11-9