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 493449308 153 PRTLSHVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGPFLQPAGTLDHHTLFMIQTPpfMKGCEHFTFHMGGPTEVLLAG 232
Cdd:cd08360    1 PRRLGHVLLFSPDVDRSVDFYRDLLGLKVSDRSFDIIAFMRGAAGSDHHLIAFAKSS--ATGLHHMSWDVSDVNEIGIGA 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 493449308 233 TRFVEKGYQSFWGPGRHRFGSNWFWYFNSPLGCHVEYDADMD--LHDDTWNA 282
Cdd:cd08360   79 SQLLRAGYKDGWGLGRHVLGSNYFHYVRDPWGSFVEYSADIDyiPDDSGWVP 130

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 493449308 153 PRTLSHVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGPFLQPAGTLDHHTLFMIQTPpfMKGCEHFTFHMGGPTEVLLAG 232
Cdd:cd08360    1 PRRLGHVLLFSPDVDRSVDFYRDLLGLKVSDRSFDIIAFMRGAAGSDHHLIAFAKSS--ATGLHHMSWDVSDVNEIGIGA 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 493449308 233 TRFVEKGYQSFWGPGRHRFGSNWFWYFNSPLGCHVEYDADMD--LHDDTWNA 282
Cdd:cd08360   79 SQLLRAGYKDGWGLGRHVLGSNYFHYVRDPWGSFVEYSADIDyiPDDSGWVP 130

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493449308 153 PRTLSHVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGpFLQPAGtlDHHTLFMIQTP-----PFMKGCEHFTFHMGGPTE 227
Cdd:COG2514    1 ITRLGHVTLRVRDLERSAAFYTDVLGLEVVEREGGRV-YLRADG--GEHLLVLEEAPgapprPGAAGLDHVAFRVPSRAD 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 493449308 228 VLLAGTRFVEKGYQsFWGPGRHRFGsnWFWYFNSPLGCHVEYDADMDLHDDTWNAREAPMGADASQL 294
Cdd:COG2514   78 LDAALARLAAAGVP-VEGAVDHGVG--ESLYFRDPDGNLIELYTDRPRFEHVGDLETDVLGFRLSDP 141

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 493449308 153 PRTLSHVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGPFLQPAGTLDHHTLFMIQTPpfMKGCEHFTFHMGGPTEVLLAG 232
Cdd:cd08360    1 PRRLGHVLLFSPDVDRSVDFYRDLLGLKVSDRSFDIIAFMRGAAGSDHHLIAFAKSS--ATGLHHMSWDVSDVNEIGIGA 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 493449308 233 TRFVEKGYQSFWGPGRHRFGSNWFWYFNSPLGCHVEYDADMD--LHDDTWNA 282
Cdd:cd08360   79 SQLLRAGYKDGWGLGRHVLGSNYFHYVRDPWGSFVEYSADIDyiPDDSGWVP 130

C-terminal, catalytic domain of BphC5 (2,3-dihydroxybiphenyl 1,2-dioxygenase); 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 C-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 493449308 153 PRTLSHVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGPFLQPAGtlDHHTLFMIQTPpfMKGCEHFTFHMGGPTEVLLAG 232
Cdd:cd07239    2 PVKLSHVVLNSPDLDKTVAFYEDVLGFRVSDWLGDVMHFLRCNS--QHHSIAIARGP--HTSLNHVAYEMRSVDEYMRGS 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 493449308 233 TRFVEKGYQSFWGPGRHRFGSNWFWYFNSPLGCHVEYDADMDLHDDTW 280
Cdd:cd07239   78 GRLIRSGARKIWGPGRHMAGDNTFSYFLDPHGNVVEYTSELELLDEDW 125

C-terminal domain of 2,3-dihydroxy-p-cumate-3,4-dioxygenase (PpCmtC); This subfamily contains the C-terminal, catalytic, domain of PpCmtC. 2,3-dihydroxy-p-cumate-3,4-dioxygenase (CmtC of Pseudomonas putida F1) is a dioxygenase involved in the eight-step catabolism pathway of p-cymene. CmtC acts upon the reaction intermediate 2,3-dihydroxy-p-cumate, yielding 2-hydroxy-3-carboxy-6-oxo-7-methylocta-2,4-dienoate. The CmtC belongs to the type I family of extradiol dioxygenases. Fe2+ was suggested as a cofactor, same as for other enzymes in the family. 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 493449308 157 SHVVYFVPDAAKAEAFYVERLGFRCTDRFtGVGPFLQPAGTldHHTLFMIQTPPfmKGCEHFTFHMGGPTEVLLAGTRFV 236
Cdd:cd07258    1 SHVGLNSTNPERDEDFWTDVCNARVSDRI-GDIFLMRVNAI--HHTFALGPASS--SGIQHINHQVTSIDDVLRSYYRLK 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 493449308 237 EKGYQSFWGPGRHRFGSNWFWYFNSPLGCHVEYDADMDLHDDTWNAREAPMGADASQL 294
Cdd:cd07258   76 EHDVPIVFGPGRHPTSGARFLYFKGPDGMTFEYSVGVDEIEDEATHRPRQFGFEPESL 133

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493449308  155 TLSHVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGPFLQPAGTLD----HHTLFMIQTPP---FMKGCEHFTFHMGGPTE 227
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKLVEETDAGEEGGLRSAFFLaggrVLELLLNETPPpaaAGFGGHHIAFIAFSVDD 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 493449308  228 VLLAGTRFVEKGYQSFWGPGRHRFGSNWFWYF 259
Cdd:pfam00903  81 VDAAYDRLKAAGVEIVREPGRHGWGGRYSYFR 112

C-terminal domain of 2,3-dihydroxybiphenyl 1,2-dioxygenase; This subfamily contains the C-terminal, catalytic, domain of BphC1-RGP6 and similar proteins. BphC catalyzes the extradiol ring cleavage reaction of 2,3-dihydroxybiphenyl, the third step in the polychlorinated biphenyls (PCBs) degradation pathway (bph pathway). This subfamily of BphCs belongs to the type I extradiol dioxygenase family, which require a metal in the active site in its catalytic mechanism. Polychlorinated biphenyl degrading bacteria demonstrate a multiplicity of BphCs. For example, three types of BphC enzymes have been found in Rhodococcus globerulus (BphC1-RGP6 - BphC3-RGP6), all three enzymes are type I extradiol dioxygenases. BphC1-RGP6 has an internal duplication, it is a two-domain dioxygenase which forms octamers, and has Fe(II) at the catalytic site. Its C-terminal repeat is represented in this subfamily. BphC2-RGP6 and BphC3-RGP6 are one-domain dioxygenases, they belong to a different subfamily of the ED_TypeI_classII_C (C-terminal domain of type I, class II extradiol dioxygenases) family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493449308 156 LSHVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGPflqPAGTLD---------HHTLFMIQtPPFMKGCEHFTFHMGGPT 226
Cdd:cd07237   10 LGHVVLIVPDVDEALAFYTDVLGFRLSDEIRIPLP---PGVTARlhflhcngrHHSLAFGA-GPGPKRLHHLMLEVTSLD 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 493449308 227 EVLLAGTRFVEKGYQSFWGPGRHrfgSN----WFwYFNSPLGCHVEYDADMDLHDDTWNARE 284
Cdd:cd07237   86 DVGRAYDRVRKRGIPIAMTLGRH---TNdkmlSF-YVATPSGFLIEYGWGGRVVDEDWTVEE 143

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 493449308 158 HVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGPFLqpAGTLDHHTLFMIQTPPFMK----GCEHFTFHMGGPTEVLLAGT 233
Cdd:cd06587    1 HVALRVPDLDASVAFYEEVLGFEVVSRNEGGGFAF--LRLGPGLRLALLEGPEPERpgggGLFHLAFEVDDVDEVDERLR 78

                         90       100
                 ....*....|....*....|....*.
gi 493449308 234 RFVEKGYQSfWGPGRHRFGSNWFWYF 259
Cdd:cd06587   79 EAGAEGELV-APPVDDPWGGRSFYFR 103

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 493449308 158 HVVYFVPDAAKAEAFYVERLGFRCTDRFTGVGPFlqPAGTLDHHTLFMIQTPPfmKGCEHFTFHMGGPTEVLLAGTRFVE 237
Cdd:cd16360    1 YAELGVPDLEKALEFYTDVLGLQVAKRDGNSVYL--RGYEDEHHSLVLYEAPE--AGLKHFAFEVASEEDLERAAASLTA 76

                         90       100       110
                 ....*....|....*....|....*....|.
gi 493449308 238 KGYQSFWGPGRHRFGSNWFWYFNSPLGCHVE 268
Cdd:cd16360   77 LGCDVTWGPDGEVPGGGKGFRFQDPSGHLLE 107