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   27-MAR-2024, entry version 204.
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; Pseudomonadota; 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 a 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; 511145-b3635; -.
DR   EnsemblBacteria; AAC76659; AAC76659; b3635.
DR   GeneID; 75202204; -.
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   OrthoDB; 9800855at2; -.
DR   PhylomeDB; P05523; -.
DR   BioCyc; EcoCyc:EG10329-MONOMER; -.
DR   BioCyc; MetaCyc:EG10329-MONOMER; -.
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:0005737; C:cytoplasm; IC:EcoCyc.
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:DNA damage response; IDA:EcoliWiki.
DR   CDD; cd08966; EcFpg-like_N; 1.
DR   Gene3D; 1.10.8.50; -; 1.
DR   Gene3D; 3.20.190.10; MutM-like, N-terminal; 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_uS13-like_H2TH.
DR   InterPro; IPR000214; Znf_DNA_glyclase/AP_lyase.
DR   InterPro; IPR010663; Znf_FPG/IleRS.
DR   NCBIfam; TIGR00577; fpg; 1.
DR   PANTHER; PTHR22993:SF9; ENDONUCLEASE 8-LIKE 1; 1.
DR   PANTHER; PTHR22993; FORMAMIDOPYRIMIDINE-DNA GLYCOSYLASE; 1.
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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   SUPFAM; SSF81624; N-terminal domain of MutM-like DNA repair proteins; 1.
DR   SUPFAM; SSF46946; S13-like H2TH domain; 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
//