FPG_ECOLI
ID FPG_ECOLI Reviewed; 269 AA.
AC P05523; Q2M7U9;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Formamidopyrimidine-DNA glycosylase;
DE Short=Fapy-DNA glycosylase;
DE EC=3.2.2.23;
DE AltName: Full=DNA-(apurinic or apyrimidinic site) lyase MutM;
DE Short=AP lyase MutM;
DE EC=4.2.99.18;
GN Name=mutM; Synonyms=fpg; OrderedLocusNames=b3635, JW3610;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3319582; DOI=10.1002/j.1460-2075.1987.tb02629.x;
RA Boiteux S., O'Connor T.R., Laval J.;
RT "Formamidopyrimidine-DNA glycosylase of Escherichia coli: cloning and
RT sequencing of the fpg structural gene and overproduction of the protein.";
RL EMBO J. 6:3177-3183(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=8041620; DOI=10.1093/nar/22.13.2576;
RA Sofia H.J., Burland V., Daniels D.L., Plunkett G. III, Blattner F.R.;
RT "Analysis of the Escherichia coli genome. V. DNA sequence of the region
RT from 76.0 to 81.5 minutes.";
RL Nucleic Acids Res. 22:2576-2586(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 1-182.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=7686882; DOI=10.1006/geno.1993.1230;
RA Burland V.D., Plunkett G. III, Daniels D.L., Blattner F.R.;
RT "DNA sequence and analysis of 136 kilobases of the Escherichia coli genome:
RT organizational symmetry around the origin of replication.";
RL Genomics 16:551-561(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 181-269.
RC STRAIN=K12;
RX PubMed=2033061; DOI=10.1016/s0021-9258(18)92875-9;
RA Clementz T., Raetz C.R.H.;
RT "A gene coding for 3-deoxy-D-manno-octulosonic-acid transferase in
RT Escherichia coli. Identification, mapping, cloning, and sequencing.";
RL J. Biol. Chem. 266:9687-9696(1991).
RN [7]
RP PROTEIN SEQUENCE OF 2-24, FUNCTION, SUBUNIT, AND COFACTOR.
RX PubMed=1689309; DOI=10.1016/s0021-9258(19)39680-2;
RA Boiteux S., O'Connor T.R., Lederer F., Gouyette A., Laval J.;
RT "Homogeneous Escherichia coli FPG protein. A DNA glycosylase which excises
RT imidazole ring-opened purines and nicks DNA at apurinic/apyrimidinic
RT sites.";
RL J. Biol. Chem. 265:3916-3922(1990).
RN [8]
RP CHARACTERIZATION.
RX PubMed=8473347; DOI=10.1016/s0021-9258(18)52978-1;
RA O'Connor T.E., Graves R.J., de Murcia G., Castaing B., Laval J.;
RT "Fpg protein of Escherichia coli is a zinc finger protein whose cysteine
RT residues have a structural and/or functional role.";
RL J. Biol. Chem. 268:9063-9070(1993).
RN [9]
RP MUTAGENESIS OF GLU-3; GLU-6; ASP-107; GLU-132; ASP-160 AND GLU-174.
RX PubMed=11106507; DOI=10.1021/bi001587x;
RA Lavrukhin O.V., Lloyd R.S.;
RT "Involvement of phylogenetically conserved acidic amino acid residues in
RT catalysis by an oxidative DNA damage enzyme formamidopyrimidine
RT glycosylase.";
RL Biochemistry 39:15266-15271(2000).
RN [10]
RP FUNCTION, AND SUBSTRATES.
RX PubMed=20031487; DOI=10.1016/j.dnarep.2009.11.008;
RA Guo Y., Bandaru V., Jaruga P., Zhao X., Burrows C.J., Iwai S.,
RA Dizdaroglu M., Bond J.P., Wallace S.S.;
RT "The oxidative DNA glycosylases of Mycobacterium tuberculosis exhibit
RT different substrate preferences from their Escherichia coli counterparts.";
RL DNA Repair 9:177-190(2010).
RN [11]
RP MUTAGENESIS OF HIS-90; ARG-109; ARG-110 AND LYS-218.
RX PubMed=14607836; DOI=10.1074/jbc.m310262200;
RA Zaika E.I., Perlow R.A., Matz E., Broyde S., Gilboa R., Grollman A.P.,
RA Zharkov D.O.;
RT "Substrate discrimination by formamidopyrimidine-DNA glycosylase: a
RT mutational analysis.";
RL J. Biol. Chem. 279:4849-4861(2004).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-269 IN COMPLEX WITH DNA.
RX PubMed=11912217; DOI=10.1074/jbc.m202058200;
RA Gilboa R., Zharkov D.O., Golan G., Fernandes A.S., Gerchman S.E., Matz E.,
RA Kycia J.H., Grollman A.P., Shoham G.;
RT "Structure of formamidopyrimidine-DNA glycosylase covalently complexed to
RT DNA.";
RL J. Biol. Chem. 277:19811-19816(2002).
CC -!- FUNCTION: Involved in base excision repair of DNA damaged by oxidation
CC or by mutagenic agents. Acts as DNA glycosylase that recognizes and
CC removes damaged bases. Has a preference for oxidized purines, such as
CC 7,8-dihydro-8-oxoguanine (8-oxoG) and its derivatives such as
CC guanidinohydantoin:C and spiroiminodihydantoin:C, however it also acts
CC on thymine glycol:G, 5,6-dihydrouracil:G and 5-hydroxyuracil:G. Has AP
CC (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA
CC strand. Cleaves the DNA backbone by beta-delta elimination to generate
CC a single-strand break at the site of the removed base with both 3'- and
CC 5'-phosphates. Cleaves ssDNA containing an AP site.
CC {ECO:0000269|PubMed:1689309, ECO:0000269|PubMed:20031487}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of DNA containing ring-opened 7-methylguanine
CC residues, releasing 2,6-diamino-4-hydroxy-5-(N-
CC methyl)formamidopyrimidine.; EC=3.2.2.23;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)-2'-
CC deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3-
CC dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-monophospho-
CC 2'-deoxyribonucleoside-DNA + H(+); Xref=Rhea:RHEA:66592, Rhea:RHEA-
CC COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695,
CC ChEBI:CHEBI:167181; EC=4.2.99.18;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:1689309};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:1689309};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11912217,
CC ECO:0000269|PubMed:1689309}.
CC -!- DOMAIN: The zinc-finger is necessary for DNA binding.
CC -!- SIMILARITY: Belongs to the FPG family. {ECO:0000305}.
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DR EMBL; M86305; AAA03747.1; -; Genomic_DNA.
DR EMBL; X06036; CAA29431.1; -; Genomic_DNA.
DR EMBL; L10328; AAA61988.1; -; Genomic_DNA.
DR EMBL; U00039; AAB18612.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76659.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77657.1; -; Genomic_DNA.
DR EMBL; M60670; AAA24045.1; -; Genomic_DNA.
DR PIR; A30254; DGECFP.
DR RefSeq; NP_418092.1; NC_000913.3.
DR RefSeq; WP_001114543.1; NZ_LN832404.1.
DR PDB; 1K82; X-ray; 2.10 A; A/B/C/D=2-269.
DR PDBsum; 1K82; -.
DR AlphaFoldDB; P05523; -.
DR SMR; P05523; -.
DR BioGRID; 4262563; 118.
DR BioGRID; 851106; 5.
DR DIP; DIP-10286N; -.
DR IntAct; P05523; 12.
DR STRING; 511145.b3635; -.
DR ChEMBL; CHEMBL4523167; -.
DR jPOST; P05523; -.
DR PaxDb; P05523; -.
DR PRIDE; P05523; -.
DR EnsemblBacteria; AAC76659; AAC76659; b3635.
DR EnsemblBacteria; BAE77657; BAE77657; BAE77657.
DR GeneID; 946765; -.
DR KEGG; ecj:JW3610; -.
DR KEGG; eco:b3635; -.
DR PATRIC; fig|1411691.4.peg.3071; -.
DR EchoBASE; EB0325; -.
DR eggNOG; COG0266; Bacteria.
DR HOGENOM; CLU_038423_1_1_6; -.
DR InParanoid; P05523; -.
DR OMA; GVHLRMT; -.
DR PhylomeDB; P05523; -.
DR BioCyc; EcoCyc:EG10329-MON; -.
DR BioCyc; MetaCyc:EG10329-MON; -.
DR BRENDA; 3.2.2.23; 2026.
DR EvolutionaryTrace; P05523; -.
DR PRO; PR:P05523; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0034039; F:8-oxo-7,8-dihydroguanine DNA N-glycosylase activity; IDA:EcoCyc.
DR GO; GO:0140078; F:class I DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:EcoCyc.
DR GO; GO:0003684; F:damaged DNA binding; IDA:EcoliWiki.
DR GO; GO:0019104; F:DNA N-glycosylase activity; IDA:EcoliWiki.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:EcoliWiki.
DR GO; GO:0004519; F:endonuclease activity; IDA:EcoliWiki.
DR GO; GO:0046872; F:metal ion binding; IDA:EcoliWiki.
DR GO; GO:0008534; F:oxidized purine nucleobase lesion DNA N-glycosylase activity; IDA:EcoCyc.
DR GO; GO:0000703; F:oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity; IDA:EcoCyc.
DR GO; GO:0008270; F:zinc ion binding; IDA:EcoliWiki.
DR GO; GO:0006284; P:base-excision repair; IDA:EcoCyc.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:EcoliWiki.
DR Gene3D; 3.20.190.10; -; 1.
DR HAMAP; MF_00103; Fapy_DNA_glycosyl; 1.
DR InterPro; IPR015886; DNA_glyclase/AP_lyase_DNA-bd.
DR InterPro; IPR015887; DNA_glyclase_Znf_dom_DNA_BS.
DR InterPro; IPR020629; Formamido-pyr_DNA_Glyclase.
DR InterPro; IPR012319; FPG_cat.
DR InterPro; IPR035937; MutM-like_N-ter.
DR InterPro; IPR010979; Ribosomal_S13-like_H2TH.
DR InterPro; IPR000214; Znf_DNA_glyclase/AP_lyase.
DR InterPro; IPR010663; Znf_FPG/IleRS.
DR Pfam; PF01149; Fapy_DNA_glyco; 1.
DR Pfam; PF06831; H2TH; 1.
DR Pfam; PF06827; zf-FPG_IleRS; 1.
DR SMART; SM00898; Fapy_DNA_glyco; 1.
DR SMART; SM01232; H2TH; 1.
DR SUPFAM; SSF46946; SSF46946; 1.
DR SUPFAM; SSF81624; SSF81624; 1.
DR TIGRFAMs; TIGR00577; fpg; 1.
DR PROSITE; PS51068; FPG_CAT; 1.
DR PROSITE; PS01242; ZF_FPG_1; 1.
DR PROSITE; PS51066; ZF_FPG_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; DNA damage; DNA repair;
KW DNA-binding; Glycosidase; Hydrolase; Lyase; Metal-binding;
KW Multifunctional enzyme; Reference proteome; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1689309"
FT CHAIN 2..269
FT /note="Formamidopyrimidine-DNA glycosylase"
FT /id="PRO_0000170822"
FT ZN_FING 235..269
FT /note="FPG-type"
FT ACT_SITE 2
FT /note="Schiff-base intermediate with DNA"
FT ACT_SITE 3
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT ACT_SITE 57
FT /note="Proton donor; for beta-elimination activity"
FT /evidence="ECO:0000305"
FT ACT_SITE 259
FT /note="Proton donor; for delta-elimination activity"
FT /evidence="ECO:0000305"
FT BINDING 90
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000269|PubMed:11912217"
FT BINDING 109
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000269|PubMed:11912217"
FT BINDING 150
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000269|PubMed:11912217"
FT MUTAGEN 3
FT /note="E->Q: Strong decrease of glycosylase activity;
FT slight decrease of AP lyase activity."
FT /evidence="ECO:0000269|PubMed:11106507"
FT MUTAGEN 6
FT /note="E->Q: Decrease of glycosylase activity; no effect on
FT AP lyase activity."
FT /evidence="ECO:0000269|PubMed:11106507"
FT MUTAGEN 90
FT /note="H->A: Increase of substrate affinity and decrease of
FT activity."
FT /evidence="ECO:0000269|PubMed:14607836"
FT MUTAGEN 107
FT /note="D->N: No effect on glycosylase and AP lyase
FT activity."
FT /evidence="ECO:0000269|PubMed:11106507"
FT MUTAGEN 109
FT /note="R->A: Over 100-fold decrease of activity."
FT /evidence="ECO:0000269|PubMed:14607836"
FT MUTAGEN 110
FT /note="R->A: Over 100-fold increase of substrate affinity
FT and decrease of activity."
FT /evidence="ECO:0000269|PubMed:14607836"
FT MUTAGEN 132
FT /note="E->Q: Decrease of glycosylase activity; slight
FT decrease of AP lyase activity."
FT /evidence="ECO:0000269|PubMed:11106507"
FT MUTAGEN 160
FT /note="D->N: No effect on glycosylase and AP lyase
FT activity."
FT /evidence="ECO:0000269|PubMed:11106507"
FT MUTAGEN 174
FT /note="E->Q: Strong decrease of glycosylase activity;
FT slight decrease of AP lyase activity."
FT /evidence="ECO:0000269|PubMed:11106507"
FT MUTAGEN 218
FT /note="K->T: Slight increase of substrate affinity and
FT decrease of activity."
FT /evidence="ECO:0000269|PubMed:14607836"
FT HELIX 4..18
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 22..29
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:1K82"
FT HELIX 39..43
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:1K82"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 77..84
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:1K82"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:1K82"
FT HELIX 140..147
FT /evidence="ECO:0007829|PDB:1K82"
FT HELIX 154..158
FT /evidence="ECO:0007829|PDB:1K82"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:1K82"
FT HELIX 169..179
FT /evidence="ECO:0007829|PDB:1K82"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:1K82"
FT HELIX 192..211
FT /evidence="ECO:0007829|PDB:1K82"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:1K82"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:1K82"
FT STRAND 259..263
FT /evidence="ECO:0007829|PDB:1K82"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:1K82"
SQ SEQUENCE 269 AA; 30290 MW; 01826F7E0E4686EC CRC64;
MPELPEVETS RRGIEPHLVG ATILHAVVRN GRLRWPVSEE IYRLSDQPVL SVQRRAKYLL
LELPEGWIII HLGMSGSLRI LPEELPPEKH DHVDLVMSNG KVLRYTDPRR FGAWLWTKEL
EGHNVLTHLG PEPLSDDFNG EYLHQKCAKK KTAIKPWLMD NKLVVGVGNI YASESLFAAG
IHPDRLASSL SLAECELLAR VIKAVLLRSI EQGGTTLKDF LQSDGKPGYF AQELQVYGRK
GEPCRVCGTP IVATKHAQRA TFYCRQCQK
