FPG_LACLC
ID FPG_LACLC Reviewed; 273 AA.
AC P42371;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 137.
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;
OS Lactococcus lactis subsp. cremoris (Streptococcus cremoris).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Lactococcus.
OX NCBI_TaxID=1359;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-22, AND FUNCTION.
RC STRAIN=NCDO 763 / ML3;
RX PubMed=7704272; DOI=10.1099/13500872-141-2-411;
RA Duwat P., de Oliveira R., Ehrlich S.D., Boiteux S.;
RT "Repair of oxidative DNA damage in Gram-positive bacteria: the Lactococcus
RT lactis Fpg protein.";
RL Microbiology 141:411-417(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 194-273.
RC STRAIN=NCDO 763 / ML3;
RX PubMed=1514816; DOI=10.1128/aem.58.8.2674-2678.1992;
RA Duwat P., Ehrlich S.D., Gruss A.;
RT "Use of degenerate primers for polymerase chain reaction cloning and
RT sequencing of the Lactococcus lactis subsp. lactis recA gene.";
RL Appl. Environ. Microbiol. 58:2674-2678(1992).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-273 OF MUTANT GLY-2 IN COMPLEX
RP WITH SUBSTRATE ANALOG.
RX PubMed=12065399; DOI=10.1093/emboj/cdf304;
RA Serre L., Pereira de Jesus K., Boiteux S., Zelwer C., Castaing B.;
RT "Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA
RT glycosylase bound to an abasic site analogue-containing DNA.";
RL EMBO J. 21:2854-2865(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). Has AP (apurinic/apyrimidinic) lyase
CC activity and introduces nicks in the DNA strand. Cleaves the DNA
CC backbone by beta-delta elimination to generate a single-strand break at
CC the site of the removed base with both 3'- and 5'-phosphates.
CC {ECO:0000269|PubMed:7704272}.
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 Note=Binds 1 zinc ion per subunit.;
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12065399}.
CC -!- MISCELLANEOUS: The zinc finger is important for DNA binding.
CC -!- SIMILARITY: Belongs to the FPG family. {ECO:0000305}.
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DR EMBL; X74298; CAA52351.1; -; Genomic_DNA.
DR EMBL; M88106; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; S39200; S39200.
DR PDB; 1KFV; X-ray; 2.55 A; A/B=2-273.
DR PDB; 1NNJ; X-ray; 1.90 A; A=2-273.
DR PDB; 1PJI; X-ray; 1.90 A; A=2-273.
DR PDB; 1PJJ; X-ray; 1.90 A; A=2-273.
DR PDB; 1PM5; X-ray; 1.95 A; A=2-273.
DR PDB; 1TDZ; X-ray; 1.80 A; A=1-273.
DR PDB; 1XC8; X-ray; 1.95 A; A=2-273.
DR PDB; 2XZF; X-ray; 1.80 A; A=2-273.
DR PDB; 2XZU; X-ray; 1.82 A; A=2-273.
DR PDB; 3C58; X-ray; 1.90 A; A=2-273.
DR PDB; 4PCZ; X-ray; 1.70 A; A=2-273.
DR PDB; 4PD2; X-ray; 1.65 A; A=2-273.
DR PDB; 4PDG; X-ray; 2.40 A; A=2-273.
DR PDB; 4PDI; X-ray; 2.10 A; A=2-273.
DR PDB; 6H0S; X-ray; 1.75 A; A=2-273.
DR PDB; 6RNM; X-ray; 1.76 A; A=2-273.
DR PDB; 6RNO; X-ray; 2.25 A; A=2-273.
DR PDB; 6RO2; X-ray; 1.82 A; A=2-273.
DR PDB; 6ROK; X-ray; 1.95 A; A=2-273.
DR PDB; 6RP0; X-ray; 2.25 A; A=2-273.
DR PDB; 6RP7; X-ray; 2.00 A; A=2-273.
DR PDBsum; 1KFV; -.
DR PDBsum; 1NNJ; -.
DR PDBsum; 1PJI; -.
DR PDBsum; 1PJJ; -.
DR PDBsum; 1PM5; -.
DR PDBsum; 1TDZ; -.
DR PDBsum; 1XC8; -.
DR PDBsum; 2XZF; -.
DR PDBsum; 2XZU; -.
DR PDBsum; 3C58; -.
DR PDBsum; 4PCZ; -.
DR PDBsum; 4PD2; -.
DR PDBsum; 4PDG; -.
DR PDBsum; 4PDI; -.
DR PDBsum; 6H0S; -.
DR PDBsum; 6RNM; -.
DR PDBsum; 6RNO; -.
DR PDBsum; 6RO2; -.
DR PDBsum; 6ROK; -.
DR PDBsum; 6RP0; -.
DR PDBsum; 6RP7; -.
DR AlphaFoldDB; P42371; -.
DR SMR; P42371; -.
DR PRIDE; P42371; -.
DR BRENDA; 3.2.2.23; 2903.
DR EvolutionaryTrace; P42371; -.
DR GO; GO:0140078; F:class I DNA-(apurinic or apyrimidinic site) endonuclease activity; IEA:UniProtKB-EC.
DR GO; GO:0003684; F:damaged DNA binding; IEA:InterPro.
DR GO; GO:0008534; F:oxidized purine nucleobase lesion DNA N-glycosylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006284; P:base-excision repair; IEA:InterPro.
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; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7704272"
FT CHAIN 2..273
FT /note="Formamidopyrimidine-DNA glycosylase"
FT /id="PRO_0000170830"
FT ZN_FING 238..272
FT /note="FPG-type"
FT REGION 58..76
FT /note="DNA-binding"
FT REGION 162..172
FT /note="DNA-binding"
FT ACT_SITE 2
FT /note="Schiff-base intermediate with DNA"
FT /evidence="ECO:0000305"
FT ACT_SITE 3
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT ACT_SITE 58
FT /note="Proton donor; for beta-elimination activity"
FT /evidence="ECO:0000305"
FT ACT_SITE 262
FT /note="Proton donor; for delta-elimination activity"
FT /evidence="ECO:0000305"
FT BINDING 92
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT BINDING 110
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT MUTAGEN 2
FT /note="P->G: Loss of activity."
FT HELIX 4..18
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 25..29
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 38..45
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 49..56
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:4PD2"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:4PD2"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 123..129
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 144..153
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 158..163
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 173..182
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 196..215
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:1XC8"
FT TURN 227..230
FT /evidence="ECO:0007829|PDB:4PD2"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:4PD2"
FT TURN 248..250
FT /evidence="ECO:0007829|PDB:4PCZ"
FT STRAND 255..259
FT /evidence="ECO:0007829|PDB:4PD2"
FT STRAND 262..266
FT /evidence="ECO:0007829|PDB:4PD2"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:4PD2"
SQ SEQUENCE 273 AA; 31310 MW; EB16055C5E09840F CRC64;
MPELPEVETV RRELEKRIVG QKIISIEATY PRMVLTGFEQ LKKELTGKTI QGISRRGKYL
IFEIGDDFRL ISHLRMEGKY RLATLDAPRE KHDHLTMKFA DGQLIYADVR KFGTWELIST
DQVLPYFLKK KIGPEPTYDE DFDEKLFREK LRKSTKKIKP YLLEQTLVAG LGNIYVDEVL
WLAKIHPEKE TNQLIESSIH LLHDSIIEIL QKAIKLGGSS IRTYSALGST GKMQNELQVY
GKTGEKCSRC GAEIQKIKVA GRGTHFCPVC QQK
