ENDO3c

endonuclease III
ENDO3c
SMART accession number:SM00478
Description: includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases
Interpro abstract (IPR003265):

Endonuclease III (EC 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 [(PUBMED:7773744), (PUBMED:9032058)]. The structurally related DNA glycosylase MutY recognises and excises the mutational intermediate 8-oxoguanine-adenine mispair [(PUBMED:1328155)]. The 3-D structures of Escherichia coli endonuclease III [(PUBMED:1411536)] and catalytic domain of MutY [(PUBMED:9846876)] have been determined. The structures 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 the [Fe4S4] cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is referred to as a [Fe4S4] cluster loop (FCL) [(PUBMED:7664751)]. Two DNA-binding motifs have been proposed, one at either end of the interdomain groove: the helix-hairpin-helix (HhH) and FCL motifs (see IPR003651). The primary role of the iron-sulphur cluster appears to involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of the FCL motif [(PUBMED:7664751), (PUBMED:10900127)].

The HhH-GPD domain gets its name from its hallmark helix-hairpin-helix and Gly/Pro rich loop followed by a conserved aspartate. This domain is found in a diverse range of structurally related DNA repair proteins that include: endonuclease III, EC 4.2.99.18 and DNA glycosylase MutY, an A/G-specific adenine glycosylase. Both of these enzymes have a C-terminal iron-sulphur cluster loop (FCL). The methyl-CPG binding protein (MBD4) also contain a related domain that is a thymine DNA glycosylase. The family also includes DNA-3-methyladenine glycosylase II EC 3.2.2.21, 8-oxoguanine DNA glycosylases and other members of the AlkA family.

GO process:base-excision repair (GO:0006284)
Family alignment:
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There are 5020 ENDO3c domains in 5020 proteins in SMART's nrdb database.

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