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 504660182   8 SVILYVEDVNASTAFYRRALGEEPVETFEGFAVFALTEDVTLGLQARDGIDPDAVGAPGSVELSMSNATRDDVDRLHRSW 87
Cdd:cd07261    1 LVILYVDNPERSTEFYRFLLGKEPVESSPTFASFVLSGGAKLGLWSSEEVEPKVAVTGGGAELSFMVPSGEQVDEVYAEW 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 504660182  88 SELGFPMALEPTELAFGYTFVATDPDGHRLRVCA 121
Cdd:cd07261   81 KAMGIPIIQEPTTMDFGYTFVATDPDGHRLRVCC 114

phenazine resistance protein, EhpR; Phenazine resistance protein (EhpR) in Enterobacter agglomerans confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. EhpR is evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504660182   8 SVILYVEDVNASTAFYRRALGEEPVETFEGFAVFALTEDVTLGLQARDGIDPDAVGAPGSVELSMSNATRDDVDRLHRSW 87
Cdd:cd07261    1 LVILYVDNPERSTEFYRFLLGKEPVESSPTFASFVLSGGAKLGLWSSEEVEPKVAVTGGGAELSFMVPSGEQVDEVYAEW 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 504660182  88 SELGFPMALEPTELAFGYTFVATDPDGHRLRVCA 121
Cdd:cd07261   81 KAMGIPIIQEPTTMDFGYTFVATDPDGHRLRVCC 114

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504660182    9 VILYVEDVNASTAFYRRALG------EEPVETFEGFAVFALTEDVTLGLQARDGIDPDAVGaPGSVELSMSNATRDDVDR 82
Cdd:pfam00903   5 VALRVGDLEKSLDFYTDVLGfklveeTDAGEEGGLRSAFFLAGGRVLELLLNETPPPAAAG-FGGHHIAFIAFSVDDVDA 83

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 504660182   83 LHRSWSELGFPMALEPTELAFG-YTFVATDPDGHRLRV 119
Cdd:pfam00903  84 AYDRLKAAGVEIVREPGRHGWGgRYSYFRDPDGNLIEL 121

phenazine resistance protein, EhpR; Phenazine resistance protein (EhpR) in Enterobacter agglomerans confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. EhpR is evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504660182   8 SVILYVEDVNASTAFYRRALGEEPVETFEGFAVFALTEDVTLGLQARDGIDPDAVGAPGSVELSMSNATRDDVDRLHRSW 87
Cdd:cd07261    1 LVILYVDNPERSTEFYRFLLGKEPVESSPTFASFVLSGGAKLGLWSSEEVEPKVAVTGGGAELSFMVPSGEQVDEVYAEW 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 504660182  88 SELGFPMALEPTELAFGYTFVATDPDGHRLRVCA 121
Cdd:cd07261   81 KAMGIPIIQEPTTMDFGYTFVATDPDGHRLRVCC 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 504660182   8 SVILYVEDVNASTAFYRRALGEEPVETFE--GFAVFALTEDVTLGLQARDGIDPDAVGAPGSVELSMSNAtrDDVDRLHR 85
Cdd:cd06587    1 HVALRVPDLDASVAFYEEVLGFEVVSRNEggGFAFLRLGPGLRLALLEGPEPERPGGGGLFHLAFEVDDV--DEVDERLR 78

                         90       100       110
                 ....*....|....*....|....*....|....
gi 504660182  86 SWSELGFPMALEPTELAFGYTFVATDPDGHRLRV 119
Cdd:cd06587   79 EAGAEGELVAPPVDDPWGGRSFYFRDPDGNLIEF 112

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 504660182  10 ILYVEDVNASTAFYRRALG--EEPVETFEGFAVFALtEDVTLGLQARDGIDPDAVGAPGSVELsmsnatrDDVDRLHRSW 87
Cdd:cd08349    3 ILPVRDIDKTLAFYVDVLGfeVDYERPPPGYAILSR-GGVELHLFEHPGLDPAGSGVAAYIRV-------EDIDALHAEL 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 504660182  88 SELGFPMALEPTELAFGYT------FVATDPDGHRLRVCA 121
Cdd:cd08349   75 KAAGLPLFGIPRITPIEDKpwgmreFAVVDPDGNLLRFGQ 114

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504660182   8 SVILYVEDVNASTAFYRRALGEEPVETFE------GFAVFALtEDVTLGLQARDGIDPDAVGAPGSVELSMsnatrDDVD 81
Cdd:COG2764    3 TPYLVVDDAEEALEFYEDVFGFEVVFRMTdpdgkiMHAELRI-GGSVLMLSDAPPDSPAAEGNGVSLSLYV-----DDVD 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 504660182  82 RLHRSWSELGFPMALEPTELAFG-YTFVATDPDGHRLRVCA 121
Cdd:COG2764   77 ALFARLVAAGATVVMPLQDTFWGdRFGMVRDPFGVLWMINT 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 504660182   7 TSVILYVEDVNASTAFYRRALGEEP-VETFEGFAVFALTEDVTLGLQARDGIDPD--AVGAPGSVELSMSNatrDDVDRL 83
Cdd:cd07264    2 AYIVLYVDDFAASLRFYRDVLGLPPrFLHEEGEYAEFDTGETKLALFSRKEMARSggPDRRGSAFELGFEV---DDVEAT 78

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 504660182  84 HRSWSELGFPMALEPTELAFGYT-FVATDPDGHRLRVC 120
Cdd:cd07264   79 VEELVERGAEFVREPANKPWGQTvAYVRDPDGNLIEIC 116

N-terminal, non-catalytic, domain of BphC5 (2,3-dihydroxybiphenyl 1,2-dioxygenase) from Rhodococcus rhodochrous K37, and similar proteins; 2,3-dihydroxybiphenyl 1,2-dioxygenase (BphC) catalyzes the extradiol ring cleavage reaction of 2,3-dihydroxybiphenyl, the third step in the polychlorinated biphenyls (PCBs) degradation pathway (bph pathway). The enzyme contains a N-terminal and a C-terminal domain of similar structure fold, resulting from an ancient gene duplication. BphC belongs to the type I extradiol dioxygenase family, which requires a metal in the active site for its catalytic activity. Polychlorinated biphenyl degrading bacteria demonstrate multiplicity of BphCs. Bacterium Rhodococcus rhodochrous K37 has eight genes encoding BphC enzymes. This family includes the N-terminal domain of BphC5-RrK37. The crystal structure of the protein from Novosphingobium aromaticivorans has a Mn(II)in the active site, although most proteins of type I extradiol dioxygenases are activated by Fe(II).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504660182   8 SVILYVEDVNASTAFYRRALGEEPVETFEGFAVFALTED----VTLGLQARDGIDPDAVGApgsvelsmsnATRDDVDRL 83
Cdd:cd08362    6 YVALGVPDLAAEREFYTEVWGLEEVAEDDDVVYLRAEGSehhvLRLRQSDENRLDLIAFAA----------ATRADVDAL 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 504660182  84 HRSWSELGFPMALEPTEL---AFGYTFVATDPDGHRLRVCATDTT 125
Cdd:cd08362   76 AARLAAAGVRILSEPGPLddpGGGYGFRFFDPDGRTIEVSADVAA 120

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 504660182    9 VILYVEDVNASTAFYRRALG------EEPVETFEGFAVFALTEDVTLGLQARDGIDPDAVGaPGSVELSMSNATRDDVDR 82
Cdd:pfam00903   5 VALRVGDLEKSLDFYTDVLGfklveeTDAGEEGGLRSAFFLAGGRVLELLLNETPPPAAAG-FGGHHIAFIAFSVDDVDA 83

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 504660182   83 LHRSWSELGFPMALEPTELAFG-YTFVATDPDGHRLRV 119
Cdd:pfam00903  84 AYDRLKAAGVEIVREPGRHGWGgRYSYFRDPDGNLIEL 121

N-terminal domain of type I, class II extradiol dioxygenases; This family contains the N-terminal non-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 504660182   9 VILYVEDVNASTAFYRRALGEEPVETFEGFAVFALTEDVTLGLQARDGIDPdavgapGSVELSMSNATRDDVDRLHRSWS 88
Cdd:cd16360    2 AELGVPDLEKALEFYTDVLGLQVAKRDGNSVYLRGYEDEHHSLVLYEAPEA------GLKHFAFEVASEEDLERAAASLT 75

                         90       100       110
                 ....*....|....*....|....*....|...
gi 504660182  89 ELGFPMALEPTELAF--GYTFVATDPDGHRLRV 119
Cdd:cd16360   76 ALGCDVTWGPDGEVPggGKGFRFQDPSGHLLEL 108

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 504660182  11 LYVEDVNASTAFYrRALGEEPVETF--EGFAVFALTEDVTLGLQARD--------GIDPDAVGApGSVELSMSNATRDDV 80
Cdd:cd09012    6 LPVTDLEASTAFY-EALGFKKNPQFsdEHASCMVVSDNIFVMLLAHDrfktfipePIAVDAKKS-TEVLLTLSAKSRQEV 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 504660182  81 DRLHRSWSELG---FPmALEPTELAFGYTFVATDPDGHRLRVC 120
Cdd:cd09012   84 DAFVDKAVEAGgkaDP-YVNGGDEGFMYGRSFEDLDGHLWEVV 125