SMART: 35EXOc domain annotation

35EXOc 3'-5' exonuclease

SMART accession number:	SM00474
Description:	3\' -5' exonuclease proofreading domain present in DNA polymerase I, Werner syndrome helicase, RNase D and other enzymes
Interpro abstract (IPR002562):	This domain is responsible for the 3'-5' exonuclease proofreading activity of Escherichia coli DNA polymerase I (polI) and other enzymes, it catalyses the hydrolysis of unpaired or mismatched nucleotides. This domain consists of the amino-terminal half of the Klenow fragment in E. coli polI it is also found in the Werner syndrome helicase (WRN), focus forming activity 1 protein (FFA-1) and ribonuclease D (RNase D) [(PUBMED:9697700)].
GO process:	nucleobase-containing compound metabolic process (GO:0006139)
GO component:	intracellular (GO:0005622)
GO function:	3'-5' exonuclease activity (GO:0008408), nucleic acid binding (GO:0003676)
Family alignment:	View or

There are 0 35EXOc domains in 0 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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Cellular role (predicted cellular role)
Cellular role: replication
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Brautigam CA, Sun S, Piccirilli JA, Steitz TA
- Structures of normal single-stranded DNA and deoxyribo-3'-S-phosphorothiolates bound to the 3'-5' exonucleolytic active site of DNA polymerase I from Escherichia coli.
- Biochemistry. 1999; 38: 696-704
- Display abstract
- The interaction of a divalent metal ion with a leaving 3' oxygen is a central component of several proposed mechanisms of phosphoryl transfer. In support of this are recent kinetic studies showing that thiophilic metal ions (e.g., Mn2+) stimulate the hydrolysis of compounds in which sulfur takes the place of the leaving oxygen. To examine the structural basis of this phenomenon, we have solved four crystal structures of single-stranded DNA's containing either oxygen or sulfur at a 3'-bridging position bound in conjunction with various metal ions at the 3'-5' exonucleolytic active site of the Klenow fragment (KF) of DNA polymerase I from Escherichia coli. Two structures of normal ssDNA bound to KF in the presence of Zn2+ and Mn2+ or Zn2+ alone were refined at 2.6- and 2.25-A resolution, respectively. They serve as standards for comparison with other Mn2+- and Zn2+-containing structures. In these cases, Mn2+ and Zn2+ bind at metal ion site B in a nearly identical position to Mg2+ (Brautigam and Steitz (1998) J. Mol. Biol. 277, 363-377). Two structures of KF bound to a deoxyoligonucleotide that contained a 3'-bridging sulfur at the scissile phosphate were refined at 2.03-A resolution. Although the bridging sulfur compounds bind in a manner very similar to that of the normal oligonucleotides, the presence of the sulfur changes the metal ion binding properties of the active site such that Mn2+ and Zn2+ are observed at metal ion site B, but Mg2+ is not. It therefore appears that the ability of the bridging sulfur compounds to exclude nonthiophilic metal ions from metal ion site B explains the low activity of KF exonuclease on these substrates in the presence of Mg2+ (Curley et al. (1997) J. Am. Chem. Soc. 119, 12691-12692) and that the 3'-bridging atom of the substrate is influencing the binding of metal ion B prior to catalysis.
- Moser MJ, Holley WR, Chatterjee A, Mian IS
- The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains.
- Nucleic Acids Res. 1997; 25: 5110-8
- Display abstract
- Prior sequence analysis studies have suggested that bacterial ribonuclease (RNase) Ds comprise a complete domain that is found also in Homo sapiens polymyositis-scleroderma overlap syndrome 100 kDa autoantigen and Werner syndrome protein. This RNase D 3'-->5' exoribonuclease domain was predicted to have a structure and mechanism of action similar to the 3'-->5' exodeoxyibonuclease (proofreading) domain of DNA polymerases. Here, hidden Markov model (HMM) and phylogenetic studies have been used to identify and characterise other sequences that may possess this exonuclease domain. Results indicate that it is also present in the RNase T family; Borrelia burgdorferi P93 protein, an immunodominant antigen in Lyme disease; bacteriophage T4 dexA and Escherichia coli exonuclease I, processive 3'-->5' exodeoxyribonucleases that degrade single-stranded DNA; Bacillus subtilis dinG, a probable helicase involved in DNA repair and possibly replication, and peptide synthase 1; Saccharomyces cerevisiae Pab1p-dependent poly(A) nuclease PAN2 subunit, required for shortening mRNA poly(A) tails; Caenorhabditis elegans and Mus musculus CAF1, transcription factor CCR4-associated factor 1; Xenopus laevis XPMC2, prevention of mitotic catastrophe in fission yeast; Drosophila melanogaster egalitarian, oocyte specification and axis determination, and exuperantia, establishment of oocyte polarity; H.sapiens HEM45, expressed in tumour cell lines and uterus and regulated by oestrogen; and 31 open reading frames including one in Methanococcus jannaschii . Examination of a multiple sequence alignment and two three-dimensional structures of proofreading domains has allowed definition of the core sequence, structural and functional elements of this exonuclease domain.
- Braithwaite DK, Ito J
- Compilation, alignment, and phylogenetic relationships of DNA polymerases.
- Nucleic Acids Res. 1993; 21: 787-802
- Ollis DL, Brick P, Hamlin R, Xuong NG, Steitz TA
- Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP.
- Nature. 1985; 313: 762-6
- Display abstract
- The 3.3-A resolution crystal structure of the large proteolytic fragment of Escherichia coli DNA polymerase I complexed with deoxythymidine monophosphate consists of two domains, the smaller of which binds zinc-deoxythymidine monophosphate. The most striking feature of the larger domain is a deep crevice of the appropriate size and shape for binding double-stranded B-DNA. A flexible subdomain may allow the enzyme to surround completely the DNA substrate, thereby allowing processive nucleotide polymerization without enzyme dissociation.
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

3D Structures of 35EXOc domains in PDB

PDB code	Main view	Title
1d8y		Crystal structure of the complex of dna polymerase i klenow fragment with dna
1d9d		Crystall structure of the complex of dna polymerase i klenow fragment with short dna fragment carrying 2'-0- aminopropyl-rna modifications 5'-d(tcg)-ap(auc)-3'
1d9f		Crystal structure of the complex of dna polymerase i klenow fragment with dna tetramer carrying 2'-o-(3-aminopropyl)- rna modification 5'-d(tt)-ap(u)-d(t)-3'
1dpi		Structure of large fragment of escherichia coli dna polymerase i complexed with d/tmp
1kfd		Crystal structures of the klenow fragment of dna polymerase i complexed with deoxynucleoside triphosphate and pyrophosphate
1kfs		Dna polymerase i klenow fragment (e.c.2.7.7.7) mutant/dna complex
1kln		Dna polymerase i klenow fragment (e.c.2.7.7.7) mutant/dna complex
1krp		Dna polymerase i klenow fragment (e.c.2.7.7.7) mutant/dna complex
1ksp		Dna polymerase i klenow fragment (e.c.2.7.7.7) mutant/dna complex
1l3s		Crystal structure of bacillus dna polymerase i fragment complexed to 9 base pairs of duplex dna.
1l3t		Crystal structure of bacillus dna polymerase i fragment product complex with 10 base pairs of duplex dna following addition of a single dttp residue
1l3u		Crystal structure of bacillus dna polymerase i fragment product complex with 11 base pairs of duplex dna following addition of a dttp and a datp residue.
1l3v		Crystal structure of bacillus dna polymerase i fragment product complex with 15 base pairs of duplex dna following addition of dttp, datp, dctp, and dgtp residues.
1l5u		Crystal structure of bacillus dna polymerase i fragment product complex with 12 base pairs of duplex dna following addition of a dttp, a datp, and a dctp residue.
1lv5		Crystal structure of the closed conformation of bacillus dna polymerase i fragment bound to dna and dctp
1njw		Guanine-thymine mismatch at the polymerase active site
1njx		Thymine-guanine mismatch at the polymerase active site
1njy		Thymine-thymine mismatch at the polymerase active site
1njz		Cytosine-thymine mismatch at the polymerase active site
1nk0		Adenine-guanine mismatch at the polymerase active site
1nk4		Guanine-guanine mismatch at the polymerase active site
1nk5		Adenine-adenine mismatch at the polymerase active site
1nk6		Cytosine-cytosine mismatch at the polymerase active site
1nk7		Guanine-adenine mismatch at the polymerase active site
1nk8		A bacillus dna polymerase i product complex bound to a guanine-thymine mismatch after a single round of primer extension, following incorporation of dctp.
1nk9		A bacillus dna polymerase i product complex bound to a guanine-thymine mismatch after two rounds of primer extension, following incorporation of dctp and dgtp.
1nkb		A bacillus dna polymerase i product complex bound to a guanine-thymine mismatch after three rounds of primer extension, following incorporation of dctp, dgtp, and dttp.
1nkc		A bacillus dna polymerase i product complex bound to a guanine-thymine mismatch after five rounds of primer extension, following incorporation of dctp, dgtp, dttp, and datp.
1nke		A bacillus dna polymerase i product complex bound to a cytosine-thymine mismatch after a single round of primer extension, following incorporation of dctp.
1qsl		Klenow fragment complexed with single-stranded substrate and europium (iii) ion
1u45		8oxoguanine at the pre-insertion site of the polymerase active site
1u47		Cytosine-8-oxoguanine base pair at the polymerase active site
1u48		Extension of a cytosine-8-oxoguanine base pair
1u49		Adenine-8oxoguanine mismatch at the polymerase active site
1u4b		Extension of an adenine-8oxoguanine mismatch
1ua0		Aminofluorene dna adduct at the pre-insertion site of a dna polymerase
1ua1		Structure of aminofluorene adduct paired opposite cytosine at the polymerase active site.
1xc9		Structure of a high-fidelity polymerase bound to a benzo[a]pyrene adduct that blocks replication
1xwl		Bacillus stearothermophilus (newly identified strain as yet unnamed) dna polymerase fragment
1yt3		Crystal structure of escherichia coli rnase d, an exoribonuclease involved in structured rna processing
2bdp		Crystal structure of bacillus dna polymerase i fragment complexed to 9 base pairs of duplex dna
2e6l		Structure of mouse wrn exonuclease domain
2e6m		Structure of mouse werner exonuclease domain
2fbt		Wrn exonuclease
2fbv		Wrn exonuclease, mn complex
2fbx		Wrn exonuclease, mg complex
2fby		Wrn exonuclease, eu complex
2fc0		Wrn exonuclease, mn dgmp complex
2hbj		Structure of the yeast nuclear exosome component, rrp6p, reveals an interplay between the active site and the hrdc domain
2hbk		Structure of the yeast nuclear exosome component, rrp6p, reveals an interplay between the active site and the hrdc domain; protein in complex with mn
2hbl		Structure of the yeast nuclear exosome component, rrp6p, reveals an interplay between the active site and the hrdc domain; protein in complex with mn, zn, and amp
2hbm		Structure of the yeast nuclear exosome component, rrp6p, reveals an interplay between the active site and the hrdc domain; protein in complex with mn, zn, and ump
2hhq		O6-methyl-guanine:t pair in the polymerase-10 basepair position
2hhs		O6-methyl:c pair in the polymerase-10 basepair position
2hht		C:o6-methyl-guanine pair in the polymerase-2 basepair position
2hhu		C:o6-methyl-guanine in the polymerase postinsertion site (- basepair position)
2hhv		T:o6-methyl-guanine in the polymerase-2 basepair position
2hhw		Ddttp:o6-methyl-guanine pair in the polymerase active site, in the closed conformation
2hhx		O6-methyl-guanine in the polymerase template preinsertion site
2hvh		Ddctp:o6meg pair in the polymerase active site (0 position)
2hvi		Ddctp:g pair in the polymerase active site (0 position)
2hw3		T:o6-methyl-guanine pair in the polymerase postinsertion site (-1 basepair position)
2kfn		Klenow fragment with bridging-sulfur substrate and manganese
2kfz		Klenow fragment with bridging-sulfur substrate and zinc only
2kzm		Klenow fragment with normal substrate and zinc and manganese
2kzz		Klenow fragment with normal substrate and zinc only
3bdp		Dna polymerase i/dna complex
3cym		Crystal structure of protein bad_0989 from bifidobacterium adolescentis
3eyz		Cocrystal structure of bacillus fragment dna polymerase i with duplex dna (open form)
3ez5		Cocrystal structure of bacillus fragment dna polymerase i with duplex dna , dctp, and zinc (closed form).
4bdp		Crystal structure of bacillus dna polymerase i fragment complexed to 11 base pairs of duplex dna after addition of two datp residues

Links (links to other resources describing this domain)
PFAM 3_5_exonuclease
INTERPRO IPR002562