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62  structures 3732  species 1  interaction 6847  sequences 22  architectures

Family: zf-FPG_IleRS (PF06827)

Summary: Zinc finger found in FPG and IleRS

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This is the Wikipedia entry entitled "FPG IleRS zinc finger". More...

FPG IleRS zinc finger Edit Wikipedia article

zf-FPG_IleRS
PDB 1tdz EBI.jpg
Crystal structure complex between the lactococcus lactis fpg (mutm) and a fapy-dg containing DNA
Identifiers
Symbol zf-FPG_IleRS
Pfam PF06827
Pfam clan CL0167
InterPro IPR010663
SCOP 1qu2
SUPERFAMILY 1qu2

The FPG IleRS zinc finger domain represents a zinc finger domain found at the C-terminal in both DNA glycosylase/AP lyase enzymes and in isoleucyl tRNA synthetase. In these two types of enzymes, the C-terminal domain forms a zinc finger.

DNA glycosylase/AP lyase enzymes are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. These enzymes have both DNA glycosylase activity (EC) and AP lyase activity (EC).[1] Examples include formamidopyrimidine-DNA glycosylases (Fpg; MutM) and endonuclease VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidation-damaged bases (N-glycosylase activity; EC) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity; EC). Fpg has a preference for oxidised purines, excising oxidized purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). ITs AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Fpg is a monomer composed of 2 domains connected by a flexible hinge.[2] The two DNA-binding motifs (a zinc finger and the helix-two-turns-helix motifs) suggest that the oxidized base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes.[2] Fpg binds one ion of zinc at the C terminus, which contains four conserved and essential cysteines.[3] Endonuclease VIII (Nei) has the same enzyme activities as Fpg above, but with a preference for oxidized pyrimidines, such as thymine glycol, 5,6-dihydrouracil and 5,6-dihydrothymine.[4][5]

An Fpg-type zinc finger is also found at the C terminus of isoleucyl tRNA synthetase (EC).[6][7] This enzyme catalyses the attachment of isoleucine to tRNA(Ile). As IleRS can inadvertently accommodate and process structurally similar amino acids such as valine, to avoid such errors it has two additional distinct tRNA(Ile)-dependent editing activities. One activity is designated as 'pre-transfer' editing and involves the hydrolysis of activated Val-AMP. The other activity is designated 'post-transfer' editing and involves deacylation of mischarged Val-tRNA(Ile).[8]

References[edit]

  1. ^ Gilboa R, Zharkov DO, Golan G, Fernandes AS, Gerchman SE, Matz E, Kycia JH, Grollman AP, Shoham G (May 2002). "Structure of formamidopyrimidine-DNA glycosylase covalently complexed to DNA". J. Biol. Chem. 277 (22): 19811–6. doi:10.1074/jbc.M202058200. PMID 11912217. 
  2. ^ a b Sugahara M, Mikawa T, Kumasaka T, Yamamoto M, Kato R, Fukuyama K, Inoue Y, Kuramitsu S (August 2000). "Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8". EMBO J. 19 (15): 3857–69. doi:10.1093/emboj/19.15.3857. PMC 306600. PMID 10921868. 
  3. ^ O'Connor TR, Graves RJ, de Murcia G, Castaing B, Laval J (April 1993). "Fpg protein of Escherichia coli is a zinc finger protein whose cysteine residues have a structural and/or functional role". J. Biol. Chem. 268 (12): 9063–70. PMID 8473347. 
  4. ^ Zharkov DO, Golan G, Gilboa R, Fernandes AS, Gerchman SE, Kycia JH, Rieger RA, Grollman AP, Shoham G (February 2002). "Structural analysis of an Escherichia coli endonuclease VIII covalent reaction intermediate". EMBO J. 21 (4): 789–800. doi:10.1093/emboj/21.4.789. PMC 125349. PMID 11847126. 
  5. ^ Doublié S, Bandaru V, Bond JP, Wallace SS (July 2004). "The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity". Proc. Natl. Acad. Sci. U.S.A. 101 (28): 10284–9. doi:10.1073/pnas.0402051101. PMC 478564. PMID 15232006. 
  6. ^ Silvian LF, Wang J, Steitz TA (August 1999). "Insights into editing from an ile-tRNA synthetase structure with tRNAile and mupirocin". Science 285 (5430): 1074–7. doi:10.1126/science.285.5430.1074. PMID 10446055. 
  7. ^ Zhou L, Rosevear PR (November 1995). "Mutation of the carboxy terminal zinc finger of E. coli isoleucyl-tRNA synthetase alters zinc binding and aminoacylation activity". Biochem. Biophys. Res. Commun. 216 (2): 648–54. doi:10.1006/bbrc.1995.2671. PMID 7488160. 
  8. ^ Fukunaga R, Yokoyama S (June 2006). "Structural basis for substrate recognition by the editing domain of isoleucyl-tRNA synthetase". J. Mol. Biol. 359 (4): 901–12. doi:10.1016/j.jmb.2006.04.025. PMID 16697013. 

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Zinc finger found in FPG and IleRS Provide feedback

This zinc binding domain is found at the C-terminus of isoleucyl tRNA synthetase and the enzyme Formamidopyrimidine-DNA glycosylase EC:3.2.2.23.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR010663

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [PUBMED:10529348, PUBMED:15963892, PUBMED:15718139, PUBMED:17210253, PUBMED:12665246]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [PUBMED:11179890]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents a zinc finger domain found at the C-terminal in both DNA glycosylase/AP lyase enzymes and in isoleucyl tRNA synthetase. In these two types of enzymes, the C-terminal domain forms a zinc finger. Some related proteins may not bind zinc.

DNA glycosylase/AP lyase enzymes are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. These enzymes have both DNA glycosylase activity (EC) and AP lyase activity (EC) [PUBMED:11912217]. Examples include formamidopyrimidine-DNA glycosylases (Fpg; MutM) and endonuclease VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidation-damaged bases (N-glycosylase activity; EC) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity; EC). Fpg has a preference for oxidised purines, excising oxidized purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). ITs AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Fpg is a monomer composed of 2 domains connected by a flexible hinge [PUBMED:10921868]. The two DNA-binding motifs (a zinc finger and the helix-two-turns-helix motifs) suggest that the oxidized base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes [PUBMED:10921868]. Fpg binds one ion of zinc at the C terminus, which contains four conserved and essential cysteines [PUBMED:8473347]. Endonuclease VIII (Nei) has the same enzyme activities as Fpg above, but with a preference for oxidized pyrimidines, such as thymine glycol, 5,6-dihydrouracil and 5,6-dihydrothymine [PUBMED:11847126, PUBMED:15232006].

An Fpg-type zinc finger is also found at the C terminus of isoleucyl tRNA synthetase (EC) [PUBMED:10446055, PUBMED:7488160]. This enzyme catalyses the attachment of isoleucine to tRNA(Ile). As IleRS can inadvertently accommodate and process structurally similar amino acids such as valine, to avoid such errors it has two additional distinct tRNA(Ile)-dependent editing activities. One activity is designated as 'pre-transfer' editing and involves the hydrolysis of activated Val-AMP. The other activity is designated 'post-transfer' editing and involves deacylation of mischarged Val-tRNA(Ile) [PUBMED:16697013].

More information about these proteins can be found at Protein of the Month: Zinc Fingers [PUBMED:].

Gene Ontology

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Domain organisation

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Full
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Representative proteomes NCBI
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(1582)
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RP35
(915)
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  Seed
(143)
Full
(6847)
Representative proteomes NCBI
(4839)
Meta
(1582)
RP15
(441)
RP35
(915)
RP55
(1228)
RP75
(1464)
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  Seed
(143)
Full
(6847)
Representative proteomes NCBI
(4839)
Meta
(1582)
RP15
(441)
RP35
(915)
RP55
(1228)
RP75
(1464)
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Seed source: Bateman A
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 143
Number in full: 6847
Average length of the domain: 29.50 aa
Average identity of full alignment: 34 %
Average coverage of the sequence by the domain: 5.63 %

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 20.8 20.8
Trusted cut-off 20.8 20.8
Noise cut-off 20.7 20.7
Model length: 30
Family (HMM) version: 9
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Species distribution

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Interactions

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H2TH

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 zf-FPG_IleRS domain has been found. There are 62 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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