Endonuclease VIII-like 1, DNA bind; Members of this family are predominantly found in Endonuclease VIII-like 1 and adopt a glucocorticoid receptor-like fold. They allow for DNA binding.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1958797282 252 DFAAFRAWLRCYAVPGMSSLRDRHGRTIWFQGDPGPLAP 290
Cdd:pfam09292   1 DYAAFQAWLQCYNVPGMNSLRDHNGRTIWFQGDPGPLAP 39

Endonuclease VIII-like 1, DNA bind; Members of this family are predominantly found in Endonuclease VIII-like 1 and adopt a glucocorticoid receptor-like fold. They allow for DNA binding.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1958797282 252 DFAAFRAWLRCYAVPGMSSLRDRHGRTIWFQGDPGPLAP 290
Cdd:pfam09292   1 DYAAFQAWLQCYNVPGMNSLRDHNGRTIWFQGDPGPLAP 39

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 1958797282    2 PEGPELHLASHFVNEICKGLVFGGCVEKSS-VSRNPEvPFE---SSAYHISALARGKELRLTLSPlpgshppqkPLSLVF 77
Cdd:smart00898   1 PELPEVETVRRGLAPALAGRTITRVEVVRPpQLRFPD-EFAaalSGRTITSVRRRGKYLLLRLLG---------GLTLVV 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1958797282   78 RFGMSGSFQLVPAEA-LPRHAHLRFYTAPPaprLALCFVDIRRFGHWD 124
Cdd:smart00898  71 HLGMSGSLRVVPAGTpPPKHDHVRLVLDDG---TELRFNDPRRFGAVR 115

DNA-formamidopyrimidine glycosylase; All proteins in the FPG family with known functions are FAPY-DNA glycosylases that function in base excision repair. Homologous to endonuclease VIII (nei). This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282  52 RGKELRLTL-SPLPGSHppqkplslvfrFGMSGSFQLVPA-EALPRHAHLRFYTAPpapRLALCFVDIRRFGHWDPGGEW 129
Cdd:TIGR00577  57 RGKYLLFELdDGALVSH-----------LRMEGKYRLEAVpDAPDKHDHVDFLFDD---GTELRYHDPRRFGTWLLLDRG 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282 130 QpGRGPCVLLEY------ERFRENVLRNLSdKAFDRPICEALLDQRFFNGIGNYLRAEILYRLKIPPFEKARTVleALQQ 203
Cdd:TIGR00577 123 Q-VENIPLLAKLgpeplsEDFTAEYLFEKL-AKSKRKIKTALLDQRLVAGIGNIYADEVLFRAGIHPERLASSL--SKEE 198

                  ...
gi 1958797282 204 CRL 206
Cdd:TIGR00577 199 CEL 201

formamidopyrimidine-DNA glycosylase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282   1 MPEGPElhlashfVNEICKGL---VFGGCVEKSSVSRNPEV--PFESSAYhISALA---------RGKELRLTLSPLPGS 66
Cdd:PRK13945    1 MPELPE-------VETVRRGLeqlLLNFIIKGVEVLLERTIasPGGVEEF-IKGLKgsligqwqrRGKYLLASLKKEGSE 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282  67 HPPqkplSLVFRFGMSGSFQLV-PAEALPRHAHLRFYTAPPAprlALCFVDIRRFGH--WDPggewqPGRGPcvlleyer 143
Cdd:PRK13945   73 NAG----WLGVHLRMTGQFLWVeQSTPPCKHTRVRLFFEKNQ---ELRFVDIRSFGQmwWVP-----PGVSP-------- 132

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282 144 frENVLRNLS-------DKAFD------------RPICEALLDQRFFNGIGNYLRAEILYRLKIPPFEKARTV-LEALQQ 203
Cdd:PRK13945  133 --ESIITGLQklgpepfSPEFSveylkkklkkrtRSIKTALLDQSIVAGIGNIYADESLFKAGIHPTTPAGQLkKKQLER 210

                  ....
gi 1958797282 204 CRLS 207
Cdd:PRK13945  211 LREA 214

Endonuclease VIII-like 1, DNA bind; Members of this family are predominantly found in Endonuclease VIII-like 1 and adopt a glucocorticoid receptor-like fold. They allow for DNA binding.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1958797282 252 DFAAFRAWLRCYAVPGMSSLRDRHGRTIWFQGDPGPLAP 290
Cdd:pfam09292   1 DYAAFQAWLQCYNVPGMNSLRDHNGRTIWFQGDPGPLAP 39

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 1958797282    2 PEGPELHLASHFVNEICKGLVFGGCVEKSS-VSRNPEvPFE---SSAYHISALARGKELRLTLSPlpgshppqkPLSLVF 77
Cdd:smart00898   1 PELPEVETVRRGLAPALAGRTITRVEVVRPpQLRFPD-EFAaalSGRTITSVRRRGKYLLLRLLG---------GLTLVV 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1958797282   78 RFGMSGSFQLVPAEA-LPRHAHLRFYTAPPaprLALCFVDIRRFGHWD 124
Cdd:smart00898  71 HLGMSGSLRVVPAGTpPPKHDHVRLVLDDG---TELRFNDPRRFGAVR 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 1958797282   2 PEGPELHLASHFVNEICKGLVFgGCVEKSSVSRN----PEVPFESSAYHISAL-ARGKELRLTLSPlpgshppqkPLSLV 76
Cdd:cd08773     1 PELPEVELLRRKLRRALKGKRV-TRVEVSDPRRLftpaAELAAALIGRRVRGAeRRGKYLLLELSG---------GPWLV 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1958797282  77 FRFGMSGSFQLVPAE-ALPRHAHLRFYTappAPRLALCFVDIRRFGHWD 124
Cdd:cd08773    71 IHLGMTGRLRVCPEGePPPKHDRLVLRL---ANGSQLRFTDPRKFGRVE 116

bifunctional DNA-formamidopyrimidine glycosylase/DNA-(apurinic or apyrimidinic site) lyase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282  52 RGKELRLTLSplpgshppqKPLSLVFRFGMSGSFQLVPAEALPR-HAHLRFYTAPpapRLALCFVDIRRFGHWDpggeWQ 130
Cdd:PRK01103   56 RGKYLLLDLD---------DGGTLISHLGMSGSLRLLPEDTPPEkHDHVDFVLDD---GTVLRYNDPRRFGAML----LT 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282 131 PgrgpcvllEYERFRENVLRNLS----DKAFD------------RPICEALLDQRFFNGIGNYLRAEILYRLKIPPFEKA 194
Cdd:PRK01103  120 P--------KGDLEAHPLLAHLGpeplSDAFDgeylaaklrkkkTAIKPALLDQTVVVGVGNIYADEALFRAGIHPERPA 191

                         170
                  ....*....|..
gi 1958797282 195 RTVleALQQCRL 206
Cdd:PRK01103  192 GSL--SRAEAER 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958797282  52 RGKELRLTLSPlpgshppqkPLSLVFRFGMSGSFQLVPAEA-LPRHAHLRFYTAPPAprlALCFVDIRRFGHWD 124
Cdd:cd08966    56 RGKYLLFELDD---------GLVLVIHLGMTGRLLVVPPDEpPEKHDHVIFELDDGR---ELRFNDPRRFGTLL 117

formamidopyrimidine-DNA glycosylase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282   1 MPEGPELHLASHFVNEickgLVFGGCVEKSSVsRNPEVPFESSAYHISALARGKelRLTLSPLPGSH-------PPQKPL 73
Cdd:PRK14810    1 MPELPEVETVARGLAP----RAAGRRIATAEF-RNLRIPRKGDPDLMAARLAGR--KILSVKRVGKHivadlegPGEPRG 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958797282  74 SLVFRFGMSGSFQLV-PAEALPRHAHLRfytAPPAPRLALCFVDIRRFGHWDPGGEW-----QPGRGPcVLLEYERFREN 147
Cdd:PRK14810   74 QWIIHLGMTGKLLLGgPDTPSPKHTHAV---LTLSSGKELRFVDSRQFGCIEYSEAFpkrfaRPGPEP-LEISFEDFAAL 149

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958797282 148 VLRNlsdkafDRPICEALLDQRFFNGIGNYLRAEILYRLKIPP--------FEKARTVLEALQQ 203
Cdd:PRK14810  150 FRGR------KTRIKSALLNQTLLRGVGNIYADEALFRAGIRPqrlasslsRERLRKLHDAIGE 207

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_4 domain, most enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zinc-finger motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958797282  75 LVFRFGMSGSFQLVPA-EALPRHAHLRFYTAPPAprlALCFVDIRRFGHWDP 125
Cdd:cd08976    69 LVMHFGMTGKLDYYPDdEDPPKHARLLLHFEDGF---RLAFECPRKFGRVRL 117