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Description:
Formamidopyrimidine-DNA glycosylase (EC 3.2.2.23) (Fapy-DNAglycosylase) (DNA-(apurinic or apyrimidinic site) lyase mutM)(EC 4.2.99.18) (AP lyase mutM).
Molecular weight: 30159
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) base-excision repair( GO:0006284 )
Important dates:
01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
16-AUG-2004, sequence version 2.
07-MAR-2006, entry version 68.
Phylogenetic order:
Bacteria Proteobacteria Gammaproteobacteria Enterobacteriales Enterobacteriaceae Escherichia.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein FPG_ECOLI:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | M86305 | AAA03747.1 | - |
| EMBL | X06036 | CAA29431.1 | - |
| EMBL | L10328 | AAA61988.1 | - |
| EMBL | U00039 | AAB18612.1 | - |
| EMBL | U00096 | AAC76659.1 | - |
| EMBL | M60670 | AAA24045.1 | - |
| PIR | A30254 | DGECFP. | |
| PDB | 1K82 | X-ray | A/B/C/D=1-268. |
| GenomeReviews | U00096_GR | b3635.1 | |
| EchoBASE | EB0325 | -.1 | |
| EcoGene | EG10329 | mutM. | |
| BioCyc | EcoCyc:EG10329-MONOMER | -.1 | |
| HAMAP | MF_00103 | - | 1. |
| InterPro | IPR000191 | Fapy_DNA_glyco. | |
| InterPro | IPR012319 | Form_DNAglyc_cat. | |
| InterPro | IPR000214 | Fpg_Zn_BS. | |
| InterPro | IPR010663 | Znf_Fpg. | |
| Pfam | PF01149 | Fapy_DNA_glyco | 1. |
| Pfam | PF06831 | H2TH | 1. |
| Pfam | PF06827 | zf-FPG_IleRS | 1. |
| ProDom | PD003680 | Fapy_DNA_glyco | 1. |
| TIGRFAMs | TIGR00577 | fpg | 1. |
| PROSITE | PS51068 | FPG_CAT | 1. |
| PROSITE | PS01242 | ZF_FPG_1 | 1. |
| PROSITE | PS51066 | ZF_FPG_2 | 1. |
Keywords:
3D-structure; Complete proteome; Direct protein sequencing; DNA damage; DNA repair; DNA-binding; Glycosidase; Hydrolase; Lyase; Metal-binding; Multifunctional enzyme; Zinc; Zinc-finger.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX MEDLINE=88082692; PubMed=3319582;
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
RT protein.";
RL EMBO J. 6:3177-3183(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / MG1655;
RX MEDLINE=94316500; PubMed=8041620;
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
RT region from 76.0 to 81.5 minutes.";
RL Nucleic Acids Res. 22:2576-2586(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-181.
RC STRAIN=K12 / MG1655;
RX MEDLINE=93315143; PubMed=7686882;
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
RT genome: organizational symmetry around the origin of replication.";
RL Genomics 16:551-561(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 180-268.
RC STRAIN=K12;
RX MEDLINE=91236744; PubMed=2033061;
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 [5]
RP PROTEIN SEQUENCE OF 1-23, FUNCTION, SUBUNIT, AND COFACTOR.
RX MEDLINE=90154076; PubMed=1689309;
RA Boiteux S., O'Connor T.R., Lederer F., Gouyette A., Laval J.;
RT "Homogeneous Escherichia coli FPG protein. A DNA glycosylase which
RT excises imidazole ring-opened purines and nicks DNA at
RT apurinic/apyrimidinic sites.";
RL J. Biol. Chem. 265:3916-3922(1990).
RN [6]
RP CHARACTERIZATION.
RX MEDLINE=93232071; PubMed=8473347;
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
RT cysteine residues have a structural and/or functional role.";
RL J. Biol. Chem. 268:9063-9070(1993).
RN [7]
RP MUTAGENESIS OF GLU-2; GLU-5; ASP-106; GLU-131; ASP-159 AND GLU-173.
RX MEDLINE=20560606; PubMed=11106507; DOI=10.1021/bi001587x;
RA Lavrukhin O.V., Lloyd R.S.;
RT "Involvement of phylogenetically conserved acidic amino acid residues
RT in catalysis by an oxidative DNA damage enzyme formamidopyrimidine
RT glycosylase.";
RL Biochemistry 39:15266-15271(2000).
RN [8]
RP MUTAGENESIS OF HIS-89; ARG-108; ARG-109 AND LYS-217.
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 [9]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-268 IN COMPLEX WITH DNA.
RX MEDLINE=22028108; PubMed=11912217; DOI=10.1074/jbc.M202058200;
RA Gilboa R., Zharkov D.O., Golan G., Fernandes A.S., Gerchman S.E.,
RA Matz E., Kycia J.H., Grollman A.P., Shoham G.;
RT "Structure of formamidopyrimidine-DNA glycosylase covalently complexed
RT to DNA.";
RL J. Biol. Chem. 277:19811-19816(2002).
Feature:
INIT_MET 0 0
CHAIN 1 268 Formamidopyrimidine-DNA glycosylase.
/FTId=PRO_0000170822.
ZN_FING 234 268 FPG-type.
ACT_SITE 1 1 Schiff-base intermediate with DNA.
ACT_SITE 2 2 Proton donor (Probable).
ACT_SITE 56 56 Proton donor (in beta-elimination)
(Probable).
ACT_SITE 258 258 Proton donor (in delta-elimination)
(Probable).
BINDING 89 89 DNA.
BINDING 108 108 DNA.
BINDING 149 149 DNA.
MUTAGEN 2 2 E->Q: Strong decrease of glycosylase
activity; slight decrease of AP lyase
activity.
MUTAGEN 5 5 E->Q: Decrease of glycosylase activity;
no effect on AP lyase activity.
MUTAGEN 89 89 H->A: Increase of substrate affinity and
decrease of activity.
MUTAGEN 106 106 D->N: No effect on glycosylase and AP
lyase activity.
MUTAGEN 108 108 R->A: Over 100-fold decrease of activity.
MUTAGEN 109 109 R->A: Over 100-fold increase of substrate
affinity and decrease of activity.
MUTAGEN 131 131 E->Q: Decrease of glycosylase activity;
slight decrease of AP lyase activity.
MUTAGEN 159 159 D->N: No effect on glycosylase and AP
lyase activity.
MUTAGEN 173 173 E->Q: Strong decrease of glycosylase
activity; slight decrease of AP lyase
activity.
MUTAGEN 217 217 K->T: Slight increase of substrate
affinity and decrease of activity.
HELIX 3 17
STRAND 18 18
TURN 19 19
STRAND 21 28
STRAND 31 35
HELIX 38 42
STRAND 45 48
STRAND 50 54
TURN 55 56
STRAND 57 61
STRAND 63 64
STRAND 66 70
TURN 72 74
STRAND 76 83
TURN 88 89
STRAND 92 96
TURN 97 98
STRAND 99 99
STRAND 101 105
STRAND 107 108
STRAND 112 117
STRAND 119 122
HELIX 123 125
TURN 126 127
TURN 132 133
STRAND 134 134
TURN 135 136
STRAND 137 137
HELIX 139 146
TURN 147 148
STRAND 151 152
HELIX 153 157
TURN 158 158
TURN 160 162
STRAND 164 165
HELIX 168 178
TURN 179 179
TURN 182 183
STRAND 184 185
HELIX 186 188
HELIX 191 210
TURN 211 212
STRAND 228 228
HELIX 230 232
STRAND 234 235
TURN 236 237
TURN 239 240
STRAND 241 242
TURN 244 246
STRAND 249 249
STRAND 251 255
TURN 256 257
STRAND 258 262
TURN 264 266
Comments:
-!- FUNCTION: Involved in base excision repair of DNA damaged by
oxidation or by mutagenic agents. Acts as DNA glycosylase that
recognizes and removes damaged bases. Has a preference for
oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has
AP (apurinic/apyrimidinic) lyase activity and introduces nicks in
the DNA strand. Cleaves 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.
-!- CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-
methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-
methyl)formamidopyrimidine.
-!- CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or
apyrimidinic site in DNA is broken by a beta-elimination reaction,
leaving a 3'-terminal unsaturated sugar and a product with a
terminal 5'-phosphate.
-!- COFACTOR: Binds 1 zinc ion per subunit.
-!- SUBUNIT: Monomer.
-!- DOMAIN: The zinc-finger is necessary for DNA binding.
-!- SIMILARITY: Belongs to the FPG family.
-!- SIMILARITY: Contains 1 FPG-type zinc finger.
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Sequence length: 268
PELPEVETSR RGIEPHLVGA TILHAVVRNG RLRWPVSEEI YRLSDQPVLS VQRRAKYLLL
ELPEGWIIIH LGMSGSLRIL PEELPPEKHD HVDLVMSNGK VLRYTDPRRF GAWLWTKELE
GHNVLTHLGP EPLSDDFNGE YLHQKCAKKK TAIKPWLMDN KLVVGVGNIY ASESLFAAGI
HPDRLASSLS LAECELLARV IKAVLLRSIE QGGTTLKDFL QSDGKPGYFA QELQVYGRKG
EPCRVCGTPI VATKHAQRAT FYCRQCQK