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 920500234  269 EYSVLQAWMRCYSVDGMNSLNDHNGRTIWFKGDPGPLVP 307
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 920500234  269 EYSVLQAWMRCYSVDGMNSLNDHNGRTIWFKGDPGPLVP 307
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 920500234     2 PEGPELHLASLFVNRMCEGVVFTGAVEKSE-VNKNPE--VPFCCDAYCIKAQSRGKEVRLTLTPikndasskrkiderqs 78
Cdd:smart00898   1 PELPEVETVRRGLAPALAGRTITRVEVVRPpQLRFPDefAAALSGRTITSVRRRGKYLLLRLLG---------------- 64

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 920500234    79 qqPMNVVFRFGMSGFFRFTSVDE-LPKHAHLRFYTNEtpHRVLSFEDTRRFGSW 131
Cdd:smart00898  65 --GLTLVVHLGMSGSLRVVPAGTpPPKHDHVRLVLDD--GTELRFNDPRRFGAV 114

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 920500234   89 GMSG-FFRFTSVDELPKHAHLRFYTNETphRVLSFEDTRRFGSWQPngswqknrGPCIMFEYESFRENVLSNLSDKAFD- 166
Cdd:TIGR00577  75 RMEGkYRLEAVPDAPDKHDHVDFLFDDG--TELRYHDPRRFGTWLL--------LDRGQVENIPLLAKLGPEPLSEDFTa 144

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 920500234  167 -----------KPICEALLNQKYFNGIGNYLRAEILFRLQIPPFEKARTV 205
Cdd:TIGR00577 145 eylfeklakskRKIKTALLDQRLVAGIGNIYADEVLFRAGIHPERLASSL 194

Formamidopyrimidine-DNA glycosylase H2TH domain; Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines from damaged DNA. This family is the central domain containing the DNA-binding helix-two turn-helix domain.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 920500234  167 KPICEALLNQKYFNGIGNYLRAEILFRLQIPPFEKARTV 205
Cdd:pfam06831  24 RPIKTALLDQTLVAGLGNIYADEVLFRAGIHPERLANSL 62

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 920500234  269 EYSVLQAWMRCYSVDGMNSLNDHNGRTIWFKGDPGPLVP 307
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 920500234     2 PEGPELHLASLFVNRMCEGVVFTGAVEKSE-VNKNPE--VPFCCDAYCIKAQSRGKEVRLTLTPikndasskrkiderqs 78
Cdd:smart00898   1 PELPEVETVRRGLAPALAGRTITRVEVVRPpQLRFPDefAAALSGRTITSVRRRGKYLLLRLLG---------------- 64

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 920500234    79 qqPMNVVFRFGMSGFFRFTSVDE-LPKHAHLRFYTNEtpHRVLSFEDTRRFGSW 131
Cdd:smart00898  65 --GLTLVVHLGMSGSLRVVPAGTpPPKHDHVRLVLDD--GTELRFNDPRRFGAV 114

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 920500234   2 PEGPELHLASLFVNRMCEGVVFTGAVE---KSEVNKNPEVPFCCDAYCIK-AQSRGKEVRLTLtpikndaSSKRKIderq 77
Cdd:cd08773    1 PELPEVELLRRKLRRALKGKRVTRVEVsdpRRLFTPAAELAAALIGRRVRgAERRGKYLLLEL-------SGGPWL---- 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 920500234  78 sqqpmnvVFRFGMSGFFR-FTSVDELPKHAHLRFYTneTPHRVLSFEDTRRFGSWQ 132
Cdd:cd08773   70 -------VIHLGMTGRLRvCPEGEPPPKHDRLVLRL--ANGSQLRFTDPRKFGRVE 116

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
                 ....*....|....*....|....*....|....*....|....
gi 920500234  89 GMSGFFRFTSVDE-LPKHAHLRFYTneTPHRVLSFEDTRRFGSW 131
Cdd:cd08966   75 GMTGRLLVVPPDEpPEKHDHVIFEL--DDGRELRFNDPRRFGTL 116

Formamidopyrimidine-DNA glycosylase H2TH domain; Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines from damaged DNA. This family is the central domain containing the DNA-binding helix-two turn-helix domain.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 920500234  167 KPICEALLNQKYFNGIGNYLRAEILFRLQIPPFEKARTV 205
Cdd:pfam06831  24 RPIKTALLDQTLVAGLGNIYADEVLFRAGIHPERLANSL 62