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 499190442   7 VPELAVADLATSLGFWVNLLGFGLKYERPEEGFAYLTLGNAHSMLDQIGQsrtwetaplQRPLGRGINFEISVSDLDVPL 86
Cdd:cd08349    1 IPILPVRDIDKTLAFYVDVLGFEVDYERPPPGYAILSRGGVELHLFEHPG---------LDPAGSGVAAYIRVEDIDALH 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 499190442  87 ARLMAADWPLFLAPeeKWYRAGDHETGVRQFLVQDPDGYLVR 128
Cdd:cd08349   72 AELKAAGLPLFGIP--RITPIEDKPWGMREFAVVDPDGNLLR 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 499190442   7 VPELAVADLATSLGFWVNLLGFGLKYERPEEGFAYLTLGNAHSMLDQIGQsrtwetaplQRPLGRGINFEISVSDLDVPL 86
Cdd:cd08349    1 IPILPVRDIDKTLAFYVDVLGFEVDYERPPPGYAILSRGGVELHLFEHPG---------LDPAGSGVAAYIRVEDIDALH 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 499190442  87 ARLMAADWPLFLAPeeKWYRAGDHETGVRQFLVQDPDGYLVR 128
Cdd:cd08349   72 AELKAAGLPLFGIP--RITPIEDKPWGMREFAVVDPDGNLLR 111

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499190442   10 LAVADLATSLGFWVNLLGFGLKYERPEEGF-----AYLTLGNAHSMLDQIGQSRTwetaPLQRPLGRGINFE-ISVSDLD 83
Cdd:pfam00903   7 LRVGDLEKSLDFYTDVLGFKLVEETDAGEEgglrsAFFLAGGRVLELLLNETPPP----AAAGFGGHHIAFIaFSVDDVD 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 499190442   84 VPLARLMAADWPlFLAPEekwyraGDHETGVRQFLVQDPDGYLVRL 129
Cdd:pfam00903  83 AAYDRLKAAGVE-IVREP------GRHGWGGRYSYFRDPDGNLIEL 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 499190442   7 VPELAVADLATSLGFWVNLLGFGLKYERPEEGFAYLTLGNAHSMLDQIGQsrtwetaplQRPLGRGINFEISVSDLDVPL 86
Cdd:cd08349    1 IPILPVRDIDKTLAFYVDVLGFEVDYERPPPGYAILSRGGVELHLFEHPG---------LDPAGSGVAAYIRVEDIDALH 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 499190442  87 ARLMAADWPLFLAPeeKWYRAGDHETGVRQFLVQDPDGYLVR 128
Cdd:cd08349   72 AELKAAGLPLFGIP--RITPIEDKPWGMREFAVVDPDGNLLR 111

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 499190442   9 ELAVADLATSLGFWVNLLGFGLKYERPEEGFAYLTLGNAHSMldqigqsRTWETAPLQRPLGRGIN-FEISVSDLDVPLA 87
Cdd:cd06587    3 ALRVPDLDASVAFYEEVLGFEVVSRNEGGGFAFLRLGPGLRL-------ALLEGPEPERPGGGGLFhLAFEVDDVDEVDE 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 499190442  88 RLMAAdwplfLAPEEKWYRAGDHETGVRQFLVQDPDGYLVRL 129
Cdd:cd06587   76 RLREA-----GAEGELVAPPVDDPWGGRSFYFRDPDGNLIEF 112

Zn-dependent glyoxalase, PhnB family [Energy production and conversion];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499190442   6 LVPELAVADLATSLGFWVNLLGFGLKYERPEEG----FAYLTLGNAHSMLdqigqSRTWETAPLQRplGRGINFEISVSD 81
Cdd:COG2764    2 VTPYLVVDDAEEALEFYEDVFGFEVVFRMTDPDgkimHAELRIGGSVLML-----SDAPPDSPAAE--GNGVSLSLYVDD 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 499190442  82 LDVPLARLMAADWPLFLAPEEKWYragdhetGVRQFLVQDPDGYLVRLS 130
Cdd:COG2764   75 VDALFARLVAAGATVVMPLQDTFW-------GDRFGMVRDPFGVLWMIN 116

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 499190442   6 LVPELAVADLATSLGFWVNLLGFGLKYErpeEGF--AYLTLGNAHSMLDQIGQSRTWETAPlqrplgrgiNFEISVSDLD 83
Cdd:cd07238    2 IVANIATADPERAAAFYGDHLGLPLVMD---HGWivTFASPGNAHAQISLAREGGSGTVVP---------DLSIEVDDVD 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 499190442  84 VPLARLMAADWPLFLAP-EEKWyragdhetGVRQFLVQDPDGYLV 127
Cdd:cd07238   70 AVHARVVAAGLRIEYGPtTEAW--------GVRRFFVRDPFGRLI 106

uncharacterized subfamily of vicinal oxygen chelate (VOC) superfamily; 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 499190442   6 LVPELAVADLATSLGFWVNLLGF--GLKYERPeEGFAYLTLGNAHSMLDQIGQSRTWETAPLQRPL-GRGINFEISVSDL 82
Cdd:cd16355    1 LTPVLNVSDIPASFAWFEKVLGFqkDWDWGDP-PTFGSVGSGECEIFLCQGGQGGSLRLGPCGDALpSYGAWMSVWVDDV 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 499190442  83 DVPLARLMAADWPLFLAPEEK-WyragdhetGVRQFLVQDPDGYLVRLS 130
Cdd:cd16355   80 DALHRECRARGADIRQPPTDMpW--------GMREMHVRHPDGHRFRVG 120

Micromonospora sp. TioX and similar proteins; Micromonospora sp. TioX is encoded by a gene of the thiocoraline biosynthetic gene cluster. Thiocoraline is a thiodepsipeptide with potent antitumor activity. TioX may be involved in thiocoraline resistance or secretion. TioX belongs to vicinal oxygen chelate (VOC) superfamily that 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 499190442   6 LVPELAVADLATSLGFWVNLLGFGLK--YERPEEGF--AYLTLGNAHSMLDQIGQSRTWETAPLQRPlGRGINFEISVSD 81
Cdd:cd08355    1 VVPTLRYRDAVAAIDWLVEAFGFEERmvVPGDEGTIhhAELTFGGGGVMVGSVRDEARPDRPADAGG-HGTQSVYVAVAD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 499190442  82 LDVPLARLMAADWPLFLAPEEKWYragdhetGVRQFLVQDPDGYL 126
Cdd:cd08355   80 PDAHYERARAAGAEIVMEPTDTDY-------GSRDYSARDPEGHL 117

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499190442    9 ELAVADLATSLGFWVNLLGFG--LKYERPEEGF--AYLTLGNAHSMLDQIGQSRtwETAPLQRPLGrGIN-FEISVSDLD 83
Cdd:pfam13669   4 GIAVPDLDRALALWGALLGLGpeGDYRSEPQNVdlAFALLGDGPVEVELIQPLD--GDSPLARHGP-GLHhLAYWVDDLD 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 499190442   84 VPLARLMAADWPLFlapeEKWYRAGDHETGV 114
Cdd:pfam13669  81 AAVARLLDQGYRVA----PKGPRAGAAGRRV 107

Glyoxalase I that uses Ni(++) as cofactor; This family includes Escherichia coil and other prokaryotic glyoxalase I that uses nickel as cofactor. Glyoxalase I (also known as lactoylglutathione lyase; EC 4.4.1.5) is part of the glyoxalase system, a two-step system for detoxifying methylglyoxal, a side product of glycolysis. This system is responsible for the conversion of reactive, acyclic alpha-oxoaldehydes into the corresponding alpha-hydroxyacids and involves 2 enzymes, glyoxalase I and II. Glyoxalase I catalyses an intramolecular redox reaction of the hemithioacetal (formed from methylglyoxal and glutathione) to form the thioester, S-D-lactoylglutathione. This reaction involves the transfer of two hydrogen atoms from C1 to C2 of the methylglyoxal, and proceeds via an ene-diol intermediate. Glyoxalase I has a requirement for bound metal ions for catalysis. Eukaryotic glyoxalase I prefers the divalent cation zinc as cofactor, whereas Escherichia coil and other prokaryotic glyoxalase I uses nickel. However, eukaryotic Trypanosomatid parasites also use nickel as a cofactor, which could possibly be explained by acquiring their GLOI gene by horizontal gene transfer. Human glyoxalase I is a two-domain enzyme and it has the structure of a domain-swapped dimer with two active sites located at the dimer interface. In yeast, in various plants, insects and Plasmodia, glyoxalase I is four-domain, possibly the result of a further gene duplication and an additional gene fusing event.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499190442  10 LAVADLATSLGFWVNLLGFGL--KYERPEEGFAYLTLGNAHSMLDQ-IGQSRTWETAPLQRPLGRGiNFEISVSDLDVPL 86
Cdd:cd16358    6 LRVGDLDRSIKFYTEVLGMKLlrKRDYPEGKYTLAFVGYGDEDENTvLELTYNWGVDKYDLGTAYG-HIAIGVEDVYETC 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 499190442  87 ARLMAADWPLFLAPEEKwyragDHETGVRQFlVQDPDGYLVRL 129
Cdd:cd16358   85 ERIRKKGGKVTREPGPM-----KGGTTVIAF-VEDPDGYKIEL 121