Bleomycin binding protein (BLMA) and similar proteins; BLMA also called Bleomycin resistance protein, confers Bm resistance by directly binding to Bm. Bm is a glycopeptide antibiotic produced naturally by actinomycetes. It is a potent anti-cancer drug, which acts as a strong DNA-cutting agent, thereby causing cell death. BLMA is produced by actinomycetes to protect themselves against their own lethal compound. BLMA has two identically-folded subdomains, with the same alpha/beta fold; these two halves have no sequence similarity. BLMAs are dimers and each dimer binds to two Bm molecules at the Bm-binding pockets formed at the dimer interface; two Bm molecules are bound per dimer. BLMA belongs to a conserved domain superfamily that is found in a variety of structurally related metalloproteins, including the bleomycin resistance protein, glyoxalase I, and type I ring-cleaving dioxygenases. As for the larger superfamily, this family contains members with or without domain swapping.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763411889   8 VPELIVTRLSASLAFWVEQLGFAIAYQRAEEGFAYLDLHGAQIMLEQYDPDAgqwltaplqsPFGRGINLQIDVPAVAPI 87
Cdd:cd08349    1 IPILPVRDIDKTLAFYVDVLGFEVDYERPPPGYAILSRGGVELHLFEHPGLD----------PAGSGVAAYIRVEDIDAL 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 763411889  88 LQRLAQLGWPLFRdvEDAWYRAGDVEAGQRQFIVQDPDGYLVR 130
Cdd:cd08349   71 HAELKAAGLPLFG--IPRITPIEDKPWGMREFAVVDPDGNLLR 111

Bleomycin binding protein (BLMA) and similar proteins; BLMA also called Bleomycin resistance protein, confers Bm resistance by directly binding to Bm. Bm is a glycopeptide antibiotic produced naturally by actinomycetes. It is a potent anti-cancer drug, which acts as a strong DNA-cutting agent, thereby causing cell death. BLMA is produced by actinomycetes to protect themselves against their own lethal compound. BLMA has two identically-folded subdomains, with the same alpha/beta fold; these two halves have no sequence similarity. BLMAs are dimers and each dimer binds to two Bm molecules at the Bm-binding pockets formed at the dimer interface; two Bm molecules are bound per dimer. BLMA belongs to a conserved domain superfamily that is found in a variety of structurally related metalloproteins, including the bleomycin resistance protein, glyoxalase I, and type I ring-cleaving dioxygenases. As for the larger superfamily, this family contains members with or without domain swapping.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763411889   8 VPELIVTRLSASLAFWVEQLGFAIAYQRAEEGFAYLDLHGAQIMLEQYDPDAgqwltaplqsPFGRGINLQIDVPAVAPI 87
Cdd:cd08349    1 IPILPVRDIDKTLAFYVDVLGFEVDYERPPPGYAILSRGGVELHLFEHPGLD----------PAGSGVAAYIRVEDIDAL 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 763411889  88 LQRLAQLGWPLFRdvEDAWYRAGDVEAGQRQFIVQDPDGYLVR 130
Cdd:cd08349   71 HAELKAAGLPLFG--IPRITPIEDKPWGMREFAVVDPDGNLLR 111

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763411889   11 LIVTRLSASLAFWVEQLGFAIAYQ-----RAEEGFAYLDLHGAQIMLEQYDPDAGqwltaPLQSPFGRGINLQ-IDVPAV 84
Cdd:pfam00903   7 LRVGDLEKSLDFYTDVLGFKLVEEtdageEGGLRSAFFLAGGRVLELLLNETPPP-----AAAGFGGHHIAFIaFSVDDV 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 763411889   85 APILQRLAQLGWPLfrdvedaWYRAGDVEAGQRQFIVQDPDGYLVRL 131
Cdd:pfam00903  82 DAAYDRLKAAGVEI-------VREPGRHGWGGRYSYFRDPDGNLIEL 121

Bleomycin binding protein (BLMA) and similar proteins; BLMA also called Bleomycin resistance protein, confers Bm resistance by directly binding to Bm. Bm is a glycopeptide antibiotic produced naturally by actinomycetes. It is a potent anti-cancer drug, which acts as a strong DNA-cutting agent, thereby causing cell death. BLMA is produced by actinomycetes to protect themselves against their own lethal compound. BLMA has two identically-folded subdomains, with the same alpha/beta fold; these two halves have no sequence similarity. BLMAs are dimers and each dimer binds to two Bm molecules at the Bm-binding pockets formed at the dimer interface; two Bm molecules are bound per dimer. BLMA belongs to a conserved domain superfamily that is found in a variety of structurally related metalloproteins, including the bleomycin resistance protein, glyoxalase I, and type I ring-cleaving dioxygenases. As for the larger superfamily, this family contains members with or without domain swapping.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763411889   8 VPELIVTRLSASLAFWVEQLGFAIAYQRAEEGFAYLDLHGAQIMLEQYDPDAgqwltaplqsPFGRGINLQIDVPAVAPI 87
Cdd:cd08349    1 IPILPVRDIDKTLAFYVDVLGFEVDYERPPPGYAILSRGGVELHLFEHPGLD----------PAGSGVAAYIRVEDIDAL 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 763411889  88 LQRLAQLGWPLFRdvEDAWYRAGDVEAGQRQFIVQDPDGYLVR 130
Cdd:cd08349   71 HAELKAAGLPLFG--IPRITPIEDKPWGMREFAVVDPDGNLLR 111

Catechol 2,3-dioxygenase or related enzyme, vicinal oxygen chelate (VOC) family [Secondary metabolites biosynthesis, transport and catabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763411889  11 LIVTRLSASLAFWVEQLGFAIAYQR----AEEGFAYLDL-HGAQIMLEQYDPDAgqwltaplQSPFGRGIN-LQIDVPAV 84
Cdd:COG0346    8 LRVSDLEASLAFYTDVLGLELVKRTdfgdGGFGHAFLRLgDGTELELFEAPGAA--------PAPGGGGLHhLAFRVDDL 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 763411889  85 APILQRLAQLGWPLFRDVedawyraGDVEAGQRQFIVQDPDGYLVRLVERLGE 137
Cdd:COG0346   80 DAAYARLRAAGVEIEGEP-------RDRAYGYRSAYFRDPDGNLIELVEPPPG 125

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 763411889  10 ELIVTRLSASLAFWVEQLGFAIAYQRAEEGFAYLDL-HGAQIMLEQYDPDAgqwlTAPLQSPFGRGINLQiDVPAVAPIL 88
Cdd:cd06587    3 ALRVPDLDASVAFYEEVLGFEVVSRNEGGGFAFLRLgPGLRLALLEGPEPE----RPGGGGLFHLAFEVD-DVDEVDERL 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 763411889  89 QRLAQLGWPLFRDVEDAWyragdveaGQRQFIVQDPDGYLVRL 131
Cdd:cd06587   78 REAGAEGELVAPPVDDPW--------GGRSFYFRDPDGNLIEF 112

Lactoylglutathione lyase-related enzyme, vicinal oxygen chelate (VOC) family [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763411889  10 ELIVTRLSASLAFWVEQLGFAIAyQRAEEGFAYLDLHGaqimleqyDPDAGQWLTAPLQSPFGRGINLQIDVPAVAPILQ 89
Cdd:COG3324    9 ELPVDDLERAKAFYEEVFGWTFE-DDAGPGGDYAEFDT--------DGGQVGGLMPGAEEPGGPGWLLYFAVDDLDAAVA 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 763411889  90 RLAQLGWPLFRDVEDawyragdVEAGQRQFIVQDPDGYLVRLVER 134
Cdd:COG3324   80 RVEAAGGTVLRPPTD-------IPPWGRFAVFRDPEGNRFGLWQP 117

Mitomycin C resistance protein (MRD); Mitomycin C (MC) is a naturally occurring antibiotic, and antitumor agent used in the treatment of cancer. Its antitumor activity is exerted primarily through monofunctional and bifunctional alkylation of DNA. MRD binds to MC and functions as a component of the MC exporting system. MC is bound to MRD by a stacking interaction between a His and a Trp. MRD adopts a structural fold similar to bleomycin resistance protein, glyoxalase I, and extradiol dioxygenases; and it has binding sites at an identical location to binding sites in these evolutionarily related enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763411889  10 ELIVTRLSASLAFWvEQLGFAIAYQRAEEGFAYLDLHGA-QIMLEQYDPDAGQWLTAPLQSPFGR-GINLQIDVPA-VAP 86
Cdd:cd07235    5 AIVVEDMAKSLEFY-RKLGFEVPEEADSAPHTEAALPGGiRLALDTEETIRSYDPGWQAPTGGGRfAIAFLCPTPAeVDA 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 763411889  87 ILQRLAQLGWPLFRDVEDA-WyragdveaGQRQFIVQDPDGYLVRL 131
Cdd:cd07235   84 KYAELTGAGYEGHLKPWNApW--------GQRYAIVKDPDGNVVDL 121

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 763411889  11 LIVTRLSASLAFWVEQLGFAIAYQRAEEGF--AYLDLHGAQIM-LEQYDPdaGQWLTAPLQSPFGRGINLQidVPAVAPI 87
Cdd:cd07245    6 LACPDLERARRFYTDVLGLEEVPRPPFLKFggAWLYLGGGQQIhLVVEQN--PSELPRPEHPGRDRHPSFS--VPDLDAL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 763411889  88 LQRLAQLGWPLFRDVEDawyragdvEAGQRQFIVQDPDGYLVRL 131
Cdd:cd07245   82 KQRLKEAGIPYTESTSP--------GGGVTQLFFRDPDGNRLEF 117

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 763411889   7 LVPELIVTRLSASLAFWVEQLGFAIAYQRAeegfAYLDLHGAQIMLEQYDPDAGQWLTAPLQS-PFGRGINLQIDVPAVA 85
Cdd:cd08359    3 LGPVIVTEDVAATAAFYVKHFGFRVIFDSD----WYVSLRRAERHGFELAIMDGQHGAVPAASqTQSSGLIINFEVDDAD 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 763411889  86 PILQRLAQLGWPLFRDVEDAWYragdveaGQRQFIVQDPDGYLV 129
Cdd:cd08359   79 AEYERLTQAGLEFLEPPRDEPW-------GQRRFIVRDPNGVLI 115