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 1681158789   2 PALPVGDIKKSIGFYCDKLGFTL--VHHEDGFAVLMCNEVRIHLWEASDEGWRSRsndspvctgaesfiagTASCRIEVE 79
Cdd:cd08349     2 PILPVRDIDKTLAFYVDVLGFEVdyERPPPGYAILSRGGVELHLFEHPGLDPAGS----------------GVAAYIRVE 65

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1681158789  80 GIDELYQHIKPLGILHP----NTSLKDQWWDERDVAVIDPDNNLISFFQ 124
Cdd:cd08349    66 DIDALHAELKAAGLPLFgiprITPIEDKPWGMREFAVVDPDGNLLRFGQ 114

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 1681158789   2 PALPVGDIKKSIGFYCDKLGFTL--VHHEDGFAVLMCNEVRIHLWEASDEGWRSRsndspvctgaesfiagTASCRIEVE 79
Cdd:cd08349     2 PILPVRDIDKTLAFYVDVLGFEVdyERPPPGYAILSRGGVELHLFEHPGLDPAGS----------------GVAAYIRVE 65

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1681158789  80 GIDELYQHIKPLGILHP----NTSLKDQWWDERDVAVIDPDNNLISFFQ 124
Cdd:cd08349    66 DIDALHAELKAAGLPLFgiprITPIEDKPWGMREFAVVDPDGNLLRFGQ 114

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1681158789   3 ALPVGDIKKSIGFYCDKLGFTLVHHED-------GFAVLMCNEVRIHLweasDEGWRSRSNDSPVCTGAESFIAgtascr 75
Cdd:pfam00903   6 ALRVGDLEKSLDFYTDVLGFKLVEETDageegglRSAFFLAGGRVLEL----LLNETPPPAAAGFGGHHIAFIA------ 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1681158789  76 IEVEGIDELYQHIKPLGIlHPNTSLKDQWWDERDVAVIDPDNNLISF 122
Cdd:pfam00903  76 FSVDDVDAAYDRLKAAGV-EIVREPGRHGWGGRYSYFRDPDGNLIEL 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 1681158789   2 PALPVGDIKKSIGFYCDKLGFTL--VHHEDGFAVLMCNEVRIHLWEASDEGWRSRsndspvctgaesfiagTASCRIEVE 79
Cdd:cd08349     2 PILPVRDIDKTLAFYVDVLGFEVdyERPPPGYAILSRGGVELHLFEHPGLDPAGS----------------GVAAYIRVE 65

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1681158789  80 GIDELYQHIKPLGILHP----NTSLKDQWWDERDVAVIDPDNNLISFFQ 124
Cdd:cd08349    66 DIDALHAELKAAGLPLFgiprITPIEDKPWGMREFAVVDPDGNLLRFGQ 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1681158789   2 PALPVGDIKKSIGFYCDKLGFTLVH---HEDG---FAVLMCNEVRIHLWEASDegwrsrsnDSPVCTGaesfiaGTASCR 75
Cdd:COG2764     4 PYLVVDDAEEALEFYEDVFGFEVVFrmtDPDGkimHAELRIGGSVLMLSDAPP--------DSPAAEG------NGVSLS 69

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1681158789  76 IEVEGIDELYQHIKPLG--ILHPntsLKDQWWDERDVAVIDPDNNLISFFQ 124
Cdd:COG2764    70 LYVDDVDALFARLVAAGatVVMP---LQDTFWGDRFGMVRDPFGVLWMINT 117

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 1681158789   3 ALPVGDIKKSIGFYCDKLGFTLVH--HEDGFAVL-MCNEVRIHLWEASDEGWRSRsndspvctGAESFIAgtascrIEVE 79
Cdd:cd06587     3 ALRVPDLDASVAFYEEVLGFEVVSrnEGGGFAFLrLGPGLRLALLEGPEPERPGG--------GGLFHLA------FEVD 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1681158789  80 GIDELYQHIKPLGILHPNTSLK-DQWWDERDVAVIDPDNNLISF 122
Cdd:cd06587    69 DVDEVDERLREAGAEGELVAPPvDDPWGGRSFYFRDPDGNLIEF 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1681158789   4 LPVGDIKKSIGFYCDKLGFTLVHHED---GFAVLMCNEVRIhlweasdeGWRSRSNDSPVCTGaesfiagtASCRIEVEG 80
Cdd:COG3324    10 LPVDDLERAKAFYEEVFGWTFEDDAGpggDYAEFDTDGGQV--------GGLMPGAEEPGGPG--------WLLYFAVDD 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1681158789  81 IDELYQHIKPLG--ILHPNTSLKDqwwDERDVAVIDPDNNLISFFQ 124
Cdd:COG3324    74 LDAAVARVEAAGgtVLRPPTDIPP---WGRFAVFRDPEGNRFGLWQ 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 1681158789   3 ALPVGDIKKSIGFYCDKLGFTLVHHE--DGFAVLMC-----NEVRIHLweaSDEGWRSRSNDSPVCTGaesfiaGTASCR 75
Cdd:cd07263     3 MLYVDDQDKALDFYVEKLGFEVVEDVpmGGMRWVTVappgsPGTSLLL---EPKAHPAQMPQSPEAAG------GTPGIL 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1681158789  76 IEVEGIDELYQHIKPLGI--LHPNTslkDQWWdERDVAVIDPDNNLI 120
Cdd:cd07263    74 LATDDIDATYERLTAAGVtfVQEPT---QMGG-GRVANFRDPDGNLF 116

Human glyoxalase domain-containing protein 5 and similar proteins; Uncharacterized subfamily of VOC family contains human glyoxalase domain-containing protein 5 and similar proteins. 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 1681158789   4 LPVGDIKKSIGFYCDKLGFTLVHHEDGFAVLMCNEVRIHLWEASDEGWRSRSNDSP----VCTGAESFIAGTAScRIEVE 79
Cdd:cd07253     9 LTVKDIERTIDFYTKVLGMTVVTFKEGRKALRFGNQKINLHQKGKEFEPKASAPTPgsadLCFITETPIDEVLE-HLEAC 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1681158789  80 GIDELYQHIKPLGILHPNTSlkdqwwderdVAVIDPDNNLI 120
Cdd:cd07253    88 GVTIEEGPVKRTGALGPILS----------IYFRDPDGNLI 118

C-terminal domain of human glyoxalase domain-containing protein 4 and similar proteins; Uncharacterized subfamily of the vicinal oxygen chelate (VOC) superfamily contains human glyoxalase domain-containing protein 4 and similar proteins. VOC 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
                  ....*....|....*....|....*....|..
gi 1681158789   3 ALPVGDIKKSIGFYCDKLGFTLVHHEDGFAVL 34
Cdd:cd16357     3 SLAVSDLEKSIDYWSDLLGMKVFEKSEKSALL 34

Glyoxalase I that uses Zn(++) as cofactor; This family includes eukaryotic glyoxalase I that prefers the divalent cation zinc 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
                  ....*....|....*....|....
gi 1681158789   6 VGDIKKSIGFYCDKLGFTLVHHED 29
Cdd:cd07233     8 VKDPKKSLKFYTEVLGMKLLRKKD 31