Toxoflavin Lyase; Toxoflavin lyase (TflA) is metalloenzyme degrading toxoflavin at the presence of oxygen, Mn(II), and dithiothreitol. TflA is structurally homologous to proteins of the vicinal oxygen chelate superfamily. The structure of TflA contains fold that displays a rare rearrangement of the structural modules indicative of domain permutation. Moreover, unlike the 2-His-1-carboxylate facial triad commonly utilized by vicinal oxygen chelate dioxygenases and other dioxygen-activating non-heme Fe(II) enzymes, the metal center in TflA consists of a 1-His-2-carboxylate facial triad. Toxoflavin is an azapteridine that is toxic to various plants, fungi, animals, and bacteria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1547020777   6 LELLTANLQATKSFYQDVLELQLVEDKEDTFTVQAGATRIRF--EATEAYDRPFYHFALNIPENKFHEAKSWIQSRVPLI 83
Cdd:cd16362     3 LTLYAPNLERSLAFYTNFLGAQHVHESNDAFTVLLNVSSIQLvaAAEGTASSPFYHIAINISANHFQEGKAALSGGGELL 82

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1547020777  84 QEEGDDEvfftswNAHSLYFEDPSGNIVEFIAR 116
Cdd:cd16362    83 TENDEDQ------NASSCYVEDPSGNLIELIGR 109

Toxoflavin Lyase; Toxoflavin lyase (TflA) is metalloenzyme degrading toxoflavin at the presence of oxygen, Mn(II), and dithiothreitol. TflA is structurally homologous to proteins of the vicinal oxygen chelate superfamily. The structure of TflA contains fold that displays a rare rearrangement of the structural modules indicative of domain permutation. Moreover, unlike the 2-His-1-carboxylate facial triad commonly utilized by vicinal oxygen chelate dioxygenases and other dioxygen-activating non-heme Fe(II) enzymes, the metal center in TflA consists of a 1-His-2-carboxylate facial triad. Toxoflavin is an azapteridine that is toxic to various plants, fungi, animals, and bacteria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1547020777   6 LELLTANLQATKSFYQDVLELQLVEDKEDTFTVQAGATRIRF--EATEAYDRPFYHFALNIPENKFHEAKSWIQSRVPLI 83
Cdd:cd16362     3 LTLYAPNLERSLAFYTNFLGAQHVHESNDAFTVLLNVSSIQLvaAAEGTASSPFYHIAINISANHFQEGKAALSGGGELL 82

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1547020777  84 QEEGDDEvfftswNAHSLYFEDPSGNIVEFIAR 116
Cdd:cd16362    83 TENDEDQ------NASSCYVEDPSGNLIELIGR 109

vicinal oxygen chelate (VOC) family; The vicinal oxygen chelate (VOC) superfamily is composed of structurally related proteins with paired beta.alpha.beta.beta.beta motifs that provide a metal coordination environment with two or three open or readily accessible coordination sites to promote direct electrophilic participation of the metal ion in catalysis. VOC is found in a variety of structurally related metalloproteins, including the type I extradiol dioxygenases, glyoxalase I and a group of antibiotic resistance proteins. A bound metal ion is required for protein activities for the members of this superfamily. A variety of metal ions have been found in the catalytic centers of these proteins including Fe(II), Mn(II), Zn(II), Ni(II) and Mg(II). Type I extradiol dioxygenases catalyze the incorporation of both atoms of molecular oxygen into aromatic substrates, which results in the cleavage of aromatic rings. They are key enzymes in the degradation of aromatic compounds. Type I extradiol dioxygenases include class I and class II enzymes. Class I and II enzymes show sequence similarity; the two-domain class II enzymes evolved from a class I enzyme through gene duplication. Glyoxylase I catalyzes the glutathione-dependent inactivation of toxic methylglyoxal, requiring zinc or nickel ions for activity. The antibiotic resistance proteins in this family use a variety of mechanisms to block the function of antibiotics. Bleomycin resistance protein (BLMA) sequesters bleomycin's activity by directly binding to it. Whereas, three types of fosfomycin resistance proteins employ different mechanisms to render fosfomycin inactive by modifying the fosfomycin molecule. Although the proteins in this superfamily are functionally distinct, their structures are similar. The difference among the three dimensional structures of the three types of proteins in this superfamily is interesting from an evolutionary perspective. Both glyoxalase I and BLMA show domain swapping between subunits. However, there is no domain swapping for type 1 extradiol dioxygenases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1547020777   6 LELLTANLQATKSFYQDVLELQLVEDKED---TFTVQAGATRIRF----EATEAYDRPFYHFALNIPENKFHEAKSWIQS 78
Cdd:cd06587     2 VALRVPDLDASVAFYEEVLGFEVVSRNEGggfAFLRLGPGLRLALlegpEPERPGGGGLFHLAFEVDDVDEVDERLREAG 81

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1547020777  79 RVPLIQEEGDDEVfftsWNAHSLYFEDPSGNIVEF 113
Cdd:cd06587    82 AEGELVAPPVDDP----WGGRSFYFRDPDGNLIEF 112

uncharacterized subfamily of vicinal oxygen chelate (VOC) family; The vicinal oxygen chelate (VOC) superfamily is composed of structurally related proteins with paired beta.alpha.beta.beta.beta motifs that provide a metal coordination environment with two or three open or readily accessible coordination sites to promote direct electrophilic participation of the metal ion in catalysis. VOC domain is found in a variety of structurally related metalloproteins, including the bleomycin resistance protein, glyoxalase I, and type I ring-cleaving dioxygenases. A bound metal ion is required for protein activities for the members of this superfamily. A variety of metal ions have been found in the catalytic centers of these proteins including Fe(II), Mn(II), Zn(II), Ni(II) and Mg(II). The protein superfamily contains members with or without domain swapping. The proteins of this family share three conserved metal binding amino acids with the type I extradiol dioxygenases, which shows no domain swapping.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1547020777   8 LLTANLQATKSFYQDVLELQLVEDKEDTFTVQAG------------ATRIRFEATEAYD-RPFYHFALNIPENKFHEAKS 74
Cdd:cd08354     6 LYADDLDAAEAFYEDVLGLKPMLRSGRHAFFRLGpqvllvfdpgatSKDVRTGEVPGHGaSGHGHFAFAVPTEELAAWEA 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1547020777  75 WIQSR-VPLIQEegddevffTSWNA--HSLYFEDPSGNIVEF 113
Cdd:cd08354    86 RLEAKgVPIESY--------TQWPEggKSLYFRDPAGNLVEL 119