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 1733378265   6 QVMLYVDDVEKAKAFWTETLEFVVVSETPLaEDYVAVEVSPTKDAETSLTIMAKEFIEKH--SPEVNLGTPSLMFKEKNF 83
Cdd:cd07263     1 QVMLYVDDQDKALDFYVEKLGFEVVEDVPM-GGMRWVTVAPPGSPGTSLLLEPKAHPAQMpqSPEAAGGTPGILLATDDI 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1733378265  84 DALYSKLNDLGLT-GHDIVEMNGQRVFNFQDGQGNYFAV 121
Cdd:cd07263    80 DATYERLTAAGVTfVQEPTQMGGGRVANFRDPDGNLFAL 118

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 1733378265   6 QVMLYVDDVEKAKAFWTETLEFVVVSETPLaEDYVAVEVSPTKDAETSLTIMAKEFIEKH--SPEVNLGTPSLMFKEKNF 83
Cdd:cd07263     1 QVMLYVDDQDKALDFYVEKLGFEVVEDVPM-GGMRWVTVAPPGSPGTSLLLEPKAHPAQMpqSPEAAGGTPGILLATDDI 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1733378265  84 DALYSKLNDLGLT-GHDIVEMNGQRVFNFQDGQGNYFAV 121
Cdd:cd07263    80 DATYERLTAAGVTfVQEPTQMGGGRVANFRDPDGNLFAL 118

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1733378265   3 KLNQVMLYVDDVEKAKAFWTETLEFVVVSETPLAEDYVAVEVSPTkDAETSLTIMAKEFIEKHSPEVNL-GTPSLMFKEK 81
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKLVEETDAGEEGGLRSAFFL-AGGRVLELLLNETPPPAAAGFGGhHIAFIAFSVD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1733378265  82 NFDALYSKLNDLGLTGHDIV--EMNGQRVFNFQDGQGNYFAV 121
Cdd:pfam00903  80 DVDAAYDRLKAAGVEIVREPgrHGWGGRYSYFRDPDGNLIEL 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 1733378265   6 QVMLYVDDVEKAKAFWTETLEFVVVSETPLaEDYVAVEVSPTKDAETSLTIMAKEFIEKH--SPEVNLGTPSLMFKEKNF 83
Cdd:cd07263     1 QVMLYVDDQDKALDFYVEKLGFEVVEDVPM-GGMRWVTVAPPGSPGTSLLLEPKAHPAQMpqSPEAAGGTPGILLATDDI 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1733378265  84 DALYSKLNDLGLT-GHDIVEMNGQRVFNFQDGQGNYFAV 121
Cdd:cd07263    80 DATYERLTAAGVTfVQEPTQMGGGRVANFRDPDGNLFAL 118

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1733378265   3 KLNQVMLYVDDVEKAKAFWTETLEFVVVSETPLAEDYVAVEVSPTkDAETSLTIMAKEFIEKHSPEVNL-GTPSLMFKEK 81
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKLVEETDAGEEGGLRSAFFL-AGGRVLELLLNETPPPAAAGFGGhHIAFIAFSVD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1733378265  82 NFDALYSKLNDLGLTGHDIV--EMNGQRVFNFQDGQGNYFAV 121
Cdd:pfam00903  80 DVDAAYDRLKAAGVEIVREPgrHGWGGRYSYFRDPDGNLIEL 121

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 1733378265   7 VMLYVDDVEKAKAFWTETLEFVVVSEtplAEDYVAVEVSPTKDAETSLTimakEFIEkHSPEVNLGTPSLMFKEKNFDAL 86
Cdd:cd06587     2 VALRVPDLDASVAFYEEVLGFEVVSR---NEGGGFAFLRLGPGLRLALL----EGPE-PERPGGGGLFHLAFEVDDVDEV 73

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1733378265  87 YSKLNDLGLTG----HDIVEMNGQRVFNFQDGQGNYF 119
Cdd:cd06587    74 DERLREAGAEGelvaPPVDDPWGGRSFYFRDPDGNLI 110

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 1733378265   9 LYVDDVEKAKAFWTETLEFVVVSETPlAEDYVavevsptkdaetsltIMAKEFIEKH---SPEVNLGTPSLMF--KEKNF 83
Cdd:cd08349     4 LPVRDIDKTLAFYVDVLGFEVDYERP-PPGYA---------------ILSRGGVELHlfeHPGLDPAGSGVAAyiRVEDI 67

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1733378265  84 DALYSKLNDLGLTG------HDIVEMN-GQRVFNFQDGQGN 117
Cdd:cd08349    68 DALHAELKAAGLPLfgipriTPIEDKPwGMREFAVVDPDGN 108