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 1011022077   5 RIVPNIATDRLDDARRFYGDLIGLTIGMDYGGIVTFVGSGAVAPQISFALEGGSGTPVPELSVEVSDLDEVFRRIVEAGH 84
Cdd:cd07238     1 RIVANIATADPERAAAFYGDHLGLPLVMDHGWIVTFASPGNAHAQISLAREGGSGTVVPDLSIEVDDVDAVHARVVAAGL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1011022077  85 PIEYGPATEPWGVRRFFVGDPFGRLANILAHE 116
Cdd:cd07238    81 RIEYGPTTEAWGVRRFFVRDPFGRLINILTHV 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 1011022077   5 RIVPNIATDRLDDARRFYGDLIGLTIGMDYGGIVTFVGSGAVAPQISFALEGGSGTPVPELSVEVSDLDEVFRRIVEAGH 84
Cdd:cd07238     1 RIVANIATADPERAAAFYGDHLGLPLVMDHGWIVTFASPGNAHAQISLAREGGSGTVVPDLSIEVDDVDAVHARVVAAGL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1011022077  85 PIEYGPATEPWGVRRFFVGDPFGRLANILAHE 116
Cdd:cd07238    81 RIEYGPTTEAWGVRRFFVRDPFGRLINILTHV 112

Glyoxalase-like domain; This domain is related to the Glyoxalase domain pfam00903.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1011022077   8 PNIATDRLDDARRFYGDLIGLTIGMDYGGIVTFVGSGA----VAPQISFALEGGSGTPVPELSVEVSDLDEVFRRIVEAG 83
Cdd:pfam12681   4 PLLVVKDINISRKFYEDVLDQKIKLDFGENVSFEGGFAiqsdFKELIGIDLSIAEQSNNFELYFEVADVDAFLQKIKEIG 83

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1011022077  84 HpIEY--GPATEPWGVRRFFVGDPFGRLANI 112
Cdd:pfam12681  84 N-IEYlhELKEQPWGQRVFRFYDPDGHIIEI 113

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 1011022077   5 RIVPNIATDRLDDARRFYGDLIGLTIGMDYGGIVTFVGSGAVAPQISFALEGGSGTPVPELSVEVSDLDEVFRRIVEAGH 84
Cdd:cd07238     1 RIVANIATADPERAAAFYGDHLGLPLVMDHGWIVTFASPGNAHAQISLAREGGSGTVVPDLSIEVDDVDAVHARVVAAGL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1011022077  85 PIEYGPATEPWGVRRFFVGDPFGRLANILAHE 116
Cdd:cd07238    81 RIEYGPTTEAWGVRRFFVRDPFGRLINILTHV 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1011022077   5 RIVPNIATDRLDDARRFYGDLIGLTIGMDY---GGIVTFV----GSGAVapqisFALEGGSGTPVPE-----LSVEVSDL 72
Cdd:COG2764     1 SVTPYLVVDDAEEALEFYEDVFGFEVVFRMtdpDGKIMHAelriGGSVL-----MLSDAPPDSPAAEgngvsLSLYVDDV 75

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1011022077  73 DEVFRRIVEAGHPIEYGPATEPWGVRRFFVGDPFG 107
Cdd:COG2764    76 DALFARLVAAGATVVMPLQDTFWGDRFGMVRDPFG 110

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 1011022077  10 IATDRLDDARRFYGDLIGLTIGMDY---GGIVTFV----GSGAV-----APQISFALEGGSGTpvpELSVEVSDLDEVFR 77
Cdd:COG0346     8 LRVSDLEASLAFYTDVLGLELVKRTdfgDGGFGHAflrlGDGTElelfeAPGAAPAPGGGGLH---HLAFRVDDLDAAYA 84

                          90       100       110
                  ....*....|....*....|....*....|
gi 1011022077  78 RIVEAGHPIEYGPATEPWGVRRFFVGDPFG 107
Cdd:COG0346    85 RLRAAGVEIEGEPRDRAYGYRSAYFRDPDG 114

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 1011022077   7 VPNIATdrlddARRFYGDLIGLTIGMDYGGIVTFVGSGAVAPQISFALEGGSGT--------PVPE----LSVEVSDLDE 74
Cdd:cd16355     7 VSDIPA-----SFAWFEKVLGFQKDWDWGDPPTFGSVGSGECEIFLCQGGQGGSlrlgpcgdALPSygawMSVWVDDVDA 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1011022077  75 VFRRIVEAGHPIEYGPATEPWGVRRFFVGDPFG 107
Cdd:cd16355    82 LHRECRARGADIRQPPTDMPWGMREMHVRHPDG 114

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 1011022077   9 NIATDRLDDARRFYGDLIGLT-IGMDYGGIVTFVGSGAvAPQISFALEGGSGTPVP----ELSVEVSDLDEVFRRIVEAG 83
Cdd:cd06587     3 ALRVPDLDASVAFYEEVLGFEvVSRNEGGGFAFLRLGP-GLRLALLEGPEPERPGGgglfHLAFEVDDVDEVDERLREAG 81

                          90       100
                  ....*....|....*....|....*.
gi 1011022077  84 --HPIEYGPATEPWGVRRFFVGDPFG 107
Cdd:cd06587    82 aeGELVAPPVDDPWGGRSFYFRDPDG 107

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1011022077  10 IATDRLDDARRFYGDLIGLT----IGMDYGGIVTFVGSGAVAPQISFALEGGSGTPVPELSVE--------VSDLDEVFR 77
Cdd:pfam00903   7 LRVGDLEKSLDFYTDVLGFKlveeTDAGEEGGLRSAFFLAGGRVLELLLNETPPPAAAGFGGHhiafiafsVDDVDAAYD 86

                          90       100       110
                  ....*....|....*....|....*....|
gi 1011022077  78 RIVEAGHPIEYGPATEPWGVRRFFVGDPFG 107
Cdd:pfam00903  87 RLKAAGVEIVREPGRHGWGGRYSYFRDPDG 116

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 1011022077   7 VPNIATDRLDDARRFYGDLIGLTIGM-----DYGgivtFVGSGAVAPQISFALEGGSGTPVPELSVEVSDLDEVFRRIVE 81
Cdd:cd08349     1 IPILPVRDIDKTLAFYVDVLGFEVDYerpppGYA----ILSRGGVELHLFEHPGLDPAGSGVAAYIRVEDIDALHAELKA 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1011022077  82 AG-----HPIEYGPATEPWGVRRFFVGDPFGRL 109
Cdd:cd08349    77 AGlplfgIPRITPIEDKPWGMREFAVVDPDGNL 109

Catechol-2,3-dioxygenase [Secondary metabolites biosynthesis, transport and catabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1011022077   3 VTRIVP-NIATDRLDDARRFYGDLIGLTIGMDYGGIVTFvgsGAVAPQISFALEGGSGTPVPE-------LSVEVS---D 71
Cdd:COG2514     1 ITRLGHvTLRVRDLERSAAFYTDVLGLEVVEREGGRVYL---RADGGEHLLVLEEAPGAPPRPgaagldhVAFRVPsraD 77

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1011022077  72 LDEVFRRIVEAGHPIEygPATEPWGVRRFFVGDPFG 107
Cdd:COG2514    78 LDAALARLAAAGVPVE--GAVDHGVGESLYFRDPDG 111

uncharacterized subfamily of vicinal oxygen chelate (VOC) family; uncharacterized subfamily of vicinal oxygen chelate (VOC) family contains Vibrio cholerae VCA0619 and similar proteins. The 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 1011022077   7 VPniATDrLDDARRFYGDLiGLTIGMDYGGiVTFVGSGavapQISFALEGgsgTPVPELS------VEVSDLDEVFRRIV 80
Cdd:cd08356     7 VP--AKD-FELSKAFYQAL-GFELASEEGG-VAYFRLG----DCSFLLQD---FYEKEHAenfmmhLLVEDVDAWHQHVK 74

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1011022077  81 EAGHPIEYG-----PATEPWGVRRFFVGDPFGRLANI 112
Cdd:cd08356    75 TLGLAERYGvkvtdPTDQPWGMRDFVLTDPSGVLWRI 111

C-terminal domain of Burkholderia sp. NF100 MhqB and similar proteins; This subfamily contains the C-terminal, catalytic, domain of Burkholderia sp. NF100 MhqB and similar proteins. MhqB is a type I extradiol dioxygenase involved in the catabolism of methylhydroquinone, an intermediate in the degradation of fenitrothion. The purified enzyme has shown extradiol ring cleavage activity toward 3-methylcatechol. Fe2+ was suggested as a cofactor, the same as most other enzymes in the family. Burkholderia sp. NF100 MhqB is encoded on the plasmid pNF1. The type I family of extradiol dioxygenases contains two structurally homologous barrel-shaped domains at the N- and C-terminal. The active-site metal is located in the C-terminal barrel and plays an essential role in the catalytic mechanism.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1011022077  12 TDRLDDARRFYGDLIGLTIGMDYGGIVTFVGSGAVAPQISFALEGGSGTPVPELSVEVSDLDEVFR---RIVEAGHpiey 88
Cdd:cd08360    11 SPDVDRSVDFYRDLLGLKVSDRSFDIIAFMRGAAGSDHHLIAFAKSSATGLHHMSWDVSDVNEIGIgasQLLRAGY---- 86

                          90       100       110
                  ....*....|....*....|....*....|
gi 1011022077  89 gpaTEPWGVRR--------FFVGDPFGRLA 110
Cdd:cd08360    87 ---KDGWGLGRhvlgsnyfHYVRDPWGSFV 113

BLMT, a bleomycin resistance protein encoded on the transposon Tn5, and similar proteins; BLMT is a bleomycin (Bm) resistance protein, encoded by the ble gene on the transposon Tn5. This protein confers a survival advantage to Escherichia coli host cells. 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. BLMT has strong binding affinity to Bm and it protects against this lethal compound through drug sequestering. BLMT has two identically-folded subdomains, with the same alpha/beta fold; these two halves have no sequence similarity. BLMT is a dimer with two Bm-binding pockets formed at the dimer interface.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1011022077  69 VSDLDEVFRRIVEAGHPIEYG-------PATEPWGVRRFFVGDPFGRL 109
Cdd:cd08350    65 VDDLDALYAQWSAAGIPEDTRgiprlhpPQTQPWGIRMFALIDPDGSL 112

C-terminal domain of type I, class II extradiol dioxygenases, catalytic domain; This family contains the C-terminal, catalytic domain of type I, class II extradiol dioxygenases. Dioxygenases catalyze the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms, resulting in the cleavage of aromatic rings. Two major groups of dioxygenases have been identified according to the cleavage site; extradiol enzymes cleave the aromatic ring between a hydroxylated carbon and an adjacent non-hydroxylated carbon, whereas intradiol enzymes cleave the aromatic ring between two hydroxyl groups. Extradiol dioxygenases are classified into type I and type II enzymes. Type I extradiol dioxygenases include class I and class II enzymes. These two classes of enzymes show sequence similarity; the two-domain class II enzymes evolved from a class I enzyme through gene duplication. The extradiol dioxygenases represented in this family are type I, class II enzymes, and are composed of the N- and C-terminal domains of similar structure fold, resulting from an ancient gene duplication. The active site is located in a funnel-shaped space of the C-terminal domain. A catalytically essential metal, Fe(II) or Mn(II), presents in all the enzymes in this family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1011022077   9 NIATDRLDDARRFYGDLIGL----TIGMDYGGIVTFVGSGAVAPQISFALEGGSGTPVPELSVEVSDLDEVFR---RIVE 81
Cdd:cd08343     4 VLCSPDVEASRDFYTDVLGFrvsdRIVDPGVDGGAFLHCDRGTDHHTVALAGGPHPGLHHVAFEVHDLDDVGRghdRLRE 83

                          90       100
                  ....*....|....*....|....*..
gi 1011022077  82 AGHPIEYGPATEPWGVRRFF-VGDPFG 107
Cdd:cd08343    84 KGYKIEWGPGRHGLGSQVFDyWFDPSG 110