Formamidopyrimidine-DNA glycosylase [Replication, recombination and repair];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   2 PELPEVETTRRGIDTVITGRTLRRLVVREARMRWPIPPALPDLLAGRTVLECGRRGKYLLLRFDHG-VQIVHLGMSGSLR 80
Cdd:COG0266    1 PELPEVETVRRGLAPALVGRTITRVEVRSPRLRFPVPEDFAARLTGRRITAVERRGKYLLLELDGGlTLLIHLGMSGRLR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265  81 RVPEQEAPRKHDHVDWVFDH-AVLRLHDPRRFGAVLWHPDEagPIAAHPLLARLGIEPFDPRFDGRWLHAYFRGRRVAIK 159
Cdd:COG0266   81 VVPPGEPPEKHDHVRLVLDDgTELRFADPRRFGALELLTPD--ELEVHPLLARLGPEPLDPDFDPEYLAARLRRRRRPIK 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 704383265 160 QALLAGDAVVGVGNIYASESLFRAGIDPRTAAQRVSAARCDRL 202
Cdd:COG0266  159 ALLLDQSVVAGVGNIYADEALFRAGIHPLRPAGSLSRAELERL 201

N-terminal domain of Escherichia coli Fpg1/MutM and related bacterial DNA glycosylases; This family contains the N-terminal domain of Escherichia coli Fpg1/MutM and related bacterial DNA glycosylases. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. Escherichia coli Fpg mainly recognizes and excises damaged purines such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). It is bifunctional, having both a DNA glycosylase (recognition activity) and a AP lyase activity. In addition to this EcFpg-like_N domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zinc-finger motif, which also contribute residues to the active site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   2 PELPEVETTRRGIDTVITGRTLRRLVVREARMRWP-IPPALPDLLAGRTVLECGRRGKYLLLRFDHGVQ-IVHLGMSGSL 79
Cdd:cd08966    1 PELPEVETVRRGLAPHLVGRRIEDVEVRRPKLRRPpDPEEFAERLVGRRITGVERRGKYLLFELDDGLVlVIHLGMTGRL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 704383265  80 RRVPEQEAPRKHDHVDWVFDH-AVLRLHDPRRFGAVLWHP 118
Cdd:cd08966   81 LVVPPDEPPEKHDHVIFELDDgRELRFNDPRRFGTLLLVP 120

Formamidopyrimidine-DNA glycosylase N-terminal domain; This entry represents the catalytic domain of DNA glycosylase/AP lyase enzymes, which are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Most damage to bases in DNA is repaired by the base excision repair pathway. These enzymes are primarily from bacteria, and have both DNA glycosylase activity and AP lyase activity. 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; ) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity; ). 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. 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. Fpg binds one ion of zinc at the C-terminus, which contains four conserved and essential cysteines.. 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. These protein contains three structural domains: an N-terminal catalytic core domain, a central helix-two turn-helix (H2TH) module and a C-terminal zinc finger (see PDB:1K82). The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. Residues that contact DNA are located in the catalytic domain and in a beta-hairpin loop formed by the zinc finger.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265     2 PELPEVETTRRGIDTVITGRTLRRL-VVREARMRWPIPPAlpDLLAGRTVLECGRRGKYLLLRFDHGVQ-IVHLGMSGSL 79
Cdd:smart00898   1 PELPEVETVRRGLAPALAGRTITRVeVVRPPQLRFPDEFA--AALSGRTITSVRRRGKYLLLRLLGGLTlVVHLGMSGSL 78

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 704383265    80 RRVPEQEAPRKHDHVDWVF-DHAVLRLHDPRRFGAVL 115
Cdd:smart00898  79 RVVPAGTPPPKHDHVRLVLdDGTELRFNDPRRFGAVR 115

Formamidopyrimidine-DNA glycosylase [Replication, recombination and repair];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   2 PELPEVETTRRGIDTVITGRTLRRLVVREARMRWPIPPALPDLLAGRTVLECGRRGKYLLLRFDHG-VQIVHLGMSGSLR 80
Cdd:COG0266    1 PELPEVETVRRGLAPALVGRTITRVEVRSPRLRFPVPEDFAARLTGRRITAVERRGKYLLLELDGGlTLLIHLGMSGRLR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265  81 RVPEQEAPRKHDHVDWVFDH-AVLRLHDPRRFGAVLWHPDEagPIAAHPLLARLGIEPFDPRFDGRWLHAYFRGRRVAIK 159
Cdd:COG0266   81 VVPPGEPPEKHDHVRLVLDDgTELRFADPRRFGALELLTPD--ELEVHPLLARLGPEPLDPDFDPEYLAARLRRRRRPIK 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 704383265 160 QALLAGDAVVGVGNIYASESLFRAGIDPRTAAQRVSAARCDRL 202
Cdd:COG0266  159 ALLLDQSVVAGVGNIYADEALFRAGIHPLRPAGSLSRAELERL 201

N-terminal domain of Escherichia coli Fpg1/MutM and related bacterial DNA glycosylases; This family contains the N-terminal domain of Escherichia coli Fpg1/MutM and related bacterial DNA glycosylases. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. Escherichia coli Fpg mainly recognizes and excises damaged purines such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). It is bifunctional, having both a DNA glycosylase (recognition activity) and a AP lyase activity. In addition to this EcFpg-like_N domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zinc-finger motif, which also contribute residues to the active site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   2 PELPEVETTRRGIDTVITGRTLRRLVVREARMRWP-IPPALPDLLAGRTVLECGRRGKYLLLRFDHGVQ-IVHLGMSGSL 79
Cdd:cd08966    1 PELPEVETVRRGLAPHLVGRRIEDVEVRRPKLRRPpDPEEFAERLVGRRITGVERRGKYLLFELDDGLVlVIHLGMTGRL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 704383265  80 RRVPEQEAPRKHDHVDWVFDH-AVLRLHDPRRFGAVLWHP 118
Cdd:cd08966   81 LVVPPDEPPEKHDHVIFELDDgRELRFNDPRRFGTLLLVP 120

formamidopyrimidine-DNA glycosylase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   1 MPELPEVETTRRGIDTVITGRTLRRLVVRE-ARMRwpippaLPDLLAGRTVLECGRRGKYLLLRFDHGVQ-IVHLGMSGS 78
Cdd:PRK14811   1 MPELPEVETTRRKLEPLLLGQTIQQVVHDDpARYR------NTELAEGRRVLGLSRRGKYLLLHLPHDLElIVHLGMTGG 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265  79 LRRvpeqeAPRKHDHVDWVFDHAVLRLHDPRRFGAvlWHPDEAGPIAAHPLLARLGIEPFDPRFDgrwLHAYFRG--RRV 156
Cdd:PRK14811  75 FRL-----EPGPHTRVTLELPGRTLYFTDPRRFGK--WWVVRAGDYREIPLLARMGPEPLSDDFT---EPEFVRAlaTAR 144

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 704383265 157 AIKQALLAGDAVVGVGNIYASESLFRAGIDPRTAAQRVSAARCDRL 202
Cdd:PRK14811 145 PVKPWLLSQKPVAGVGNIYADESLWRARIHPARPATSLKAPEARRL 190

Formamidopyrimidine-DNA glycosylase N-terminal domain; This entry represents the catalytic domain of DNA glycosylase/AP lyase enzymes, which are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Most damage to bases in DNA is repaired by the base excision repair pathway. These enzymes are primarily from bacteria, and have both DNA glycosylase activity and AP lyase activity. 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; ) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity; ). 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. 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. Fpg binds one ion of zinc at the C-terminus, which contains four conserved and essential cysteines.. 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. These protein contains three structural domains: an N-terminal catalytic core domain, a central helix-two turn-helix (H2TH) module and a C-terminal zinc finger (see PDB:1K82). The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. Residues that contact DNA are located in the catalytic domain and in a beta-hairpin loop formed by the zinc finger.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265     2 PELPEVETTRRGIDTVITGRTLRRL-VVREARMRWPIPPAlpDLLAGRTVLECGRRGKYLLLRFDHGVQ-IVHLGMSGSL 79
Cdd:smart00898   1 PELPEVETVRRGLAPALAGRTITRVeVVRPPQLRFPDEFA--AALSGRTITSVRRRGKYLLLRLLGGLTlVVHLGMSGSL 78

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 704383265    80 RRVPEQEAPRKHDHVDWVF-DHAVLRLHDPRRFGAVL 115
Cdd:smart00898  79 RVVPAGTPPPKHDHVRLVLdDGTELRFNDPRRFGAVR 115

N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases; DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. These enzymes initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycolsylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. The FpgNei DNA glycosylases represent one of the two structural superfamilies of DNA glycosylases that recognize oxidized bases (the other is the HTH-GPD superfamily exemplified by Escherichia coli Nth). Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. One exception is mouse Nei-like glycosylase 3 (Neil3) which forms a Schiff base intermediate via its N-terminal valine. In addition to this FpgNei_N domain, FpgNei proteins have a helix-two-turn-helix (H2TH) domain and a zinc (or zincless)-finger motif which also contribute residues to the active site. FpgNei DNA glycosylases have a broad substrate specificity. They are bifunctional, in addition to the glycosylase (recognition) activity, they have a lyase (cleaving) activity on the phosphodiester backbone of the DNA at the AP site. This superfamily includes eukaryotic, bacterial, and viral proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   2 PELPEVETTRRGIDTVITGRTLRRLVVREARMRWPIPPALPDLLAGRTVLECGRRGKYLLLRFDHGVQ-IVHLGMSGSLR 80
Cdd:cd08773    1 PELPEVELLRRKLRRALKGKRVTRVEVSDPRRLFTPAAELAAALIGRRVRGAERRGKYLLLELSGGPWlVIHLGMTGRLR 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 704383265  81 RVPEQEAPRKHDHVDWVF-DHAVLRLHDPRRFGAVLW 116
Cdd:cd08773   81 VCPEGEPPPKHDRLVLRLaNGSQLRFTDPRKFGRVEL 117

N-terminal domain of the plant and fungal Nei and related proteins; This family contains the N-terminal domain of plant and Fungi Nei and related proteins. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. The plant and fungal FpgNei glycosylases prefer the oxidized pyrimidines spiroiminodihydantoin (Sp), guanidinohydantoin (Gh) over 8-oxoguanine in double stranded oligonucleotides and also show weak activity on single stranded DNA. In addition to this domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a characteristic zincless finger motif. They share a common ancestor not shared with other eukaryotic members of the FpgNei family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   1 MPELPEVETTRRGIDTVITGRTLRRLVVREArmrwPI------PPALPDLLAGRTVLECGRRGKYLLLRFDHG--VQIVH 72
Cdd:cd08972    1 MPELPEVERARRLLEEHCLGKKITKVDAQDD----DKvfggvtPGAFQKALLGRTITSAHRKGKYFWLTLDGDapVPVMH 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265  73 LGMSGSL---------------RRVPEQEAPRKHDHVDWVFDHAV-LRLHDPRRFGAVLW 116
Cdd:cd08972   77 FGMTGAIsikgvktiyykmlrpPKEEDQTWPPRFYKFVLTLEDGTeLAFTDPRRLGRVRL 136

Uncharacterized bacterial subgroup of the N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases; This family is an uncharacterized bacterial subgroup of the FpgNei_N domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. This N-terminal proline is conserved in this family. Escherichia coli Fpg prefers 8-oxo-7,8-dihydroguanine (8-oxoG) and oxidized purines and Escherichia coli Nei recognizes oxidized pyrimidines. However, neither Escherichia coli Fpg or Nei belong to this family. In addition to this BaFpgNei_N_1 domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zinc-finger motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   1 MPELPEVETTRRGIDTVITGRTLRRLVVREARMRWPIPPaLPDLLAGRTVLECGRRGKYLLLRFDHG-VQIVHLGMSGSL 79
Cdd:cd08973    1 MPELPEVEVYAENLERRLTGKTITRVELASKSLLVTPDP-PLEALEGRTVTGVRRHGKRLDFEFDNGlHLVLHLMLAGWL 79

                         90       100
                 ....*....|....*....|....*....
gi 704383265  80 R-RVPEQEAPRKHDHV--DWVFDHAVLRL 105
Cdd:cd08973   80 YwTEAGALLPGKKGPIalRFEDYGGGLDL 108

N-terminal domain of the actinomycetal Nei2 and related DNA glycosylases; This family contains the N-terminal domain of the actinomycetal Nei2 and related DNA glycosylases. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. This family contains mostly actinomycetes and includes Mycobacterium tuberculosis Nei2 (MtuNei2). Complementation experiments in repair-deficient Escherichia coli (fpg mutY nei triple and nei nth double mutants), support that MtuNei2 is functionally active in vivo and recognizes both guanine and cytosine oxidation products. In addition to this AcNei2_N domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zinc-finger motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 704383265   1 MPELPEVETTRRGIDTVITGRTLRRlvvreARMRWPIPPALPdlLAGRTVLECGRRGKYLLLRFDHGVQI-VHLGMSGSL 79
Cdd:cd08971    1 MPEGDTVHRAARRLRRALAGRVLTR-----ADLRVPRLATAD--LAGRTVEEVVARGKHLLIRFDGGLTLhTHLRMDGSW 73

                         90
                 ....*....|....*...
gi 704383265  80 RRVPEQEAPRKHDHVDWV 97
Cdd:cd08971   74 HVYRPGERWRRPAHQARA 91