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20  structures 2745  species 1  interaction 3890  sequences 11  architectures

Family: EndIII_4Fe-2S (PF10576)

Summary: Iron-sulfur binding domain of endonuclease III

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Iron-sulfur binding domain of endonuclease III Provide feedback

Escherichia coli endonuclease III (EC 4.2.99.18) [1] is a DNA repair enzyme that acts both as a DNA N-glycosylase, removing oxidised pyrimidines from DNA, and as an apurinic/apyrimidinic (AP) endonuclease, introducing a single-strand nick at the site from which the damaged base was removed. Endonuclease III is an iron-sulfur protein that binds a single 4Fe-4S cluster. The 4Fe-4S cluster does not seem to be important for catalytic activity, but is probably involved in the proper positioning of the enzyme along the DNA strand [2]. The 4Fe-4S cluster is bound by four cysteines which are all located in a 17 amino acid region at the C-terminal end of endonuclease III. A similar region is also present in the central section of mutY and in the C-terminus of ORF-10 and of the Micro-coccus UV endonuclease [4].

Literature references

  1. Thayer MM, Ahern H, Xing D, Cunningham RP, Tainer JA; , EMBO J. 1995;14:4108-4120.: Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure. PUBMED:7664751 EPMC:7664751

  2. Hilbert TP, Chaung W, Boorstein RJ, Cunningham RP, Teebor GW; , J Biol Chem. 1997;272:6733-6740.: Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III. PUBMED:9045706 EPMC:9045706

  3. Watanabe T, Blaisdell JO, Wallace SS, Bond JP; , J Biol Chem. 2005;280:34378-34384.: Engineering functional changes in Escherichia coli endonuclease III based on phylogenetic and structural analyses. PUBMED:16096281 EPMC:16096281

  4. Gorodetsky AA, Boal AK, Barton JK; , J Am Chem Soc. 2006;128:12082-12083.: Direct electrochemistry of endonuclease III in the presence and absence of DNA. PUBMED:16967954 EPMC:16967954


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003651

Endonuclease III (EC) 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. 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 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.

Gene Ontology

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Domain organisation

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Alignments

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  Seed
(505)
Full
(3890)
Representative proteomes NCBI
(2381)
Meta
(391)
RP15
(236)
RP35
(509)
RP55
(651)
RP75
(789)
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Format an alignment

  Seed
(505)
Full
(3890)
Representative proteomes NCBI
(2381)
Meta
(391)
RP15
(236)
RP35
(509)
RP55
(651)
RP75
(789)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(505)
Full
(3890)
Representative proteomes NCBI
(2381)
Meta
(391)
RP15
(236)
RP35
(509)
RP55
(651)
RP75
(789)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Curation View help on the curation process

Seed source: PROSITE_PS00764
Previous IDs: none
Type: Domain
Author: Finn R, Coggill P
Number in seed: 505
Number in full: 3890
Average length of the domain: 17.00 aa
Average identity of full alignment: 50 %
Average coverage of the sequence by the domain: 6.34 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.5 19.6
Trusted cut-off 20.5 19.6
Noise cut-off 20.4 19.5
Model length: 17
Family (HMM) version: 4
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

HhH-GPD

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the EndIII_4Fe-2S domain has been found. There are 20 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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