vicinal oxygen chelate (VOC) family protein similar to Bacillus subtilis YqjT; 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 695723856   6 GVQHVGLAVSNLEESAAFFTDLL--GWQEVKRRDDYPAIFvKDGAVMLTLWKTQTEEPIQFNRKnNVGLHHLALQVETKE 83
Cdd:cd07242    1 GVSHVELAVSDLHRSFKWFEWILglGWKEYDTWSFGPSWK-LSGGSLLVVQQTDEFATPEFDRA-RVGLNHLAFHAESRE 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 695723856  84 GLYQILEVLKANQVEIEF-EPTLLREGPS-MHMMCYEPSGIRVEFYYP 129
Cdd:cd07242   79 AVDELTEKLAKIGGVRTYgDRHPFAGGPPhYAAFCEDPDGIKLELVAP 126

methylmalonyl-CoA epimerase; Members of this protein family are the enzyme methylmalonyl-CoA epimerase (EC 5.1.99.1), also called methylmalonyl-CoA racemase. This enzyme converts (2R)-methylmalonyl-CoA to (2S)-methylmalonyl-CoA, which is then a substrate for methylmalonyl-CoA mutase (TIGR00642). It is known in bacteria, archaea, and as a mitochondrial protein in animals. It is closely related to lactoylglutathione lyase (TIGR00068), which is also called glyoxylase I, and is also a homodimer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856    7 VQHVGLAVSNLEESAAFFTDLLGWQeVKRRDDYPAIFVKdgAVMLTLWKTQTE--EPIQ-------FNRKNNVGLHHLAL 77
Cdd:TIGR03081   2 IDHVGIAVPDLEEAAKFYEDVLGAQ-VSEIEELPEQGVK--VVFIALGNTKVEllEPLGedspiakFLEKNGGGIHHIAI 78

                          90       100
                  ....*....|....*....|..
gi 695723856   78 QVETKEglyQILEVLKANQVEI 99
Cdd:TIGR03081  79 EVDDIE---AALETLKEKGVRL 97

vicinal oxygen chelate (VOC) family protein similar to Bacillus subtilis YqjT; 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 695723856   6 GVQHVGLAVSNLEESAAFFTDLL--GWQEVKRRDDYPAIFvKDGAVMLTLWKTQTEEPIQFNRKnNVGLHHLALQVETKE 83
Cdd:cd07242    1 GVSHVELAVSDLHRSFKWFEWILglGWKEYDTWSFGPSWK-LSGGSLLVVQQTDEFATPEFDRA-RVGLNHLAFHAESRE 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 695723856  84 GLYQILEVLKANQVEIEF-EPTLLREGPS-MHMMCYEPSGIRVEFYYP 129
Cdd:cd07242   79 AVDELTEKLAKIGGVRTYgDRHPFAGGPPhYAAFCEDPDGIKLELVAP 126

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 695723856   9 HVGLAVSNLEESAAFFTDLLGWQEVKRRDDYPAIFVKDGA-VMLTLWKTQTEEpiqfnRKNNVGLHHLALQVETKEGLYQ 87
Cdd:cd06587    1 HVALRVPDLDASVAFYEEVLGFEVVSRNEGGGFAFLRLGPgLRLALLEGPEPE-----RPGGGGLFHLAFEVDDVDEVDE 75

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 695723856  88 ILEVLKANQVEIEFEPTLLREGPSMHmmCYEPSGIRVEF 126
Cdd:cd06587   76 RLREAGAEGELVAPPVDDPWGGRSFY--FRDPDGNLIEF 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 695723856   9 HVGLAVSNLEESAAFFTDLLGWQEVKRRDDYPAIFVKDGAVMLTLwktqTEEPiqfnRKNNVGLHHLALQVETKEGLYQI 88
Cdd:cd07254    4 HLSLNVTDLERSIRFYSDLFGAEPAKRKADYAKFMLEDPPLNLAL----LVND----RKEPYGLNHLGIQVDSKEEVAAL 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 695723856  89 LEVLKANQVEIEFEP-TLLREGPSMHMMCYEPSGIRVEFYY 128
Cdd:cd07254   76 KARAEAAGLPVRKEPrTTCCYAVQDKFWLTDPDGNAWEFYA 116

Fosfomycin resistant protein; This family contains three types of fosfomycin resistant protein. Fosfomycin inhibits the enzyme UDP-N-acetylglucosamine-3-enolpyruvyltransferase (MurA), which catalyzes the first committed step in bacterial cell wall biosynthesis. The three types of fosfomycin resistance proteins, employ different mechanisms to render fosfomycin [(1R,2S)-epoxypropylphosphonic acid] inactive. FosB catalyzes the addition of L-cysteine to the epoxide ring of fosfomycin. FosX catalyzes the addition of a water molecule to the C1 position of the antibiotic with inversion of configuration at C1. FosA catalyzes the addition of glutathione to the antibiotic fosfomycin, making it inactive. Catalytic activities of both FosX and FosA are Mn(II)-dependent, but FosB is activated by Mg(II). Fosfomycin resistant proteins are evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856   9 HVGLAVSNLEESAAFFTDLLGWQEVKRRDDYPAIFVKDGAVML-TLWKTQTEEPIQFNRKNNvglhHLALQVeTKEGLYQ 87
Cdd:cd08345    1 HITLIVRDLEKSTAFLQDIFGAREVYSSGDKTFSLSKEKFFLLgGLWIALMEGESLQERSYT----HIAFQI-QSEDFDR 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 695723856  88 ILEVLKANQVEIEFE-PTLLREGPSMHMmcYEPSGIRVEFY 127
Cdd:cd08345   76 YAERLGALGVEMRPPrPRVEGEGRSIYF--YDPDNHLFELH 114

Methylmalonyl-CoA epimerase (MMCE); MMCE, also called methylmalonyl-CoA racemase (EC 5.1.99.1) interconverts (2R)-methylmalonyl-CoA and (2S)-methylmalonyl-CoA. MMCE has been found in bacteria, archaea, and in animals. In eukaryotes, MMCE is an essential enzyme in a pathway that converts propionyl-CoA to succinyl-CoA, and is important in the breakdown of odd-chain length fatty acids, branched-chain amino acids, and other metabolites. In bacteria, MMCE participates in the reverse pathway for propionate fermentation, glyoxylate regeneration, and the biosynthesis of polyketide antibiotics. MMCE is closely related to glyoxalase I and type I extradiol dioxygenases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856   7 VQHVGLAVSNLEESAAFFTDLLGWQEVkRRDDYPAIFVKdgAVMLTLWKTQTE--EPI-------QFNRKNNVGLHHLAL 77
Cdd:cd07249    1 LDHIGIAVPDLDEALKFYEDVLGVKVS-EPEELEEQGVR--VAFLELGNTQIEllEPLgedspiaKFLDKKGGGLHHIAF 77

                 ...
gi 695723856  78 QVE 80
Cdd:cd07249   78 EVD 80

N-terminal, non-catalytic, domain of BphC_JF8, (2,3-dihydroxybiphenyl 1,2-dioxygenase) from Bacillus sp. JF8, and similar proteins; 2,3-dihydroxybiphenyl 1,2-dioxygenase (BphC) catalyzes the extradiol ring cleavage reaction of 2,3-dihydroxybiphenyl, a key step in the polychlorinated biphenyls (PCBs) degradation pathway (bph pathway). BphC belongs to the type I extradiol dioxygenase family, which requires a metal ion in the active site in its catalytic mechanism. Polychlorinated biphenyl degrading bacteria demonstrate a multiplicity of BphCs. This subfamily of BphC is represented by the enzyme purified from the thermophilic biphenyl and naphthalene degrader, Bacillus sp. JF8. The members in this family of BphC enzymes may use either Mn(II) or Fe(II) as cofactors. The enzyme purified from Bacillus sp. JF8 is Mn(II)-dependent, however, the enzyme from Rhodococcus jostii RHAI has Fe(II) bound to it. BphC_JF8 is thermostable and its optimum activity is at 85 degrees C. The enzymes in this family have an internal duplication. This family represents the N-terminal repeat.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856   2 PLTHGVQHVGLAVSNLEESAAFFTDLLGWQEVKRrddypaifvKDGAVMLTLWKTQTEEPIQFNRKNNVGLHHLALQVET 81
Cdd:cd09013    2 FDLAQLAHVELLTPKPEESLWFFTDVLGLEETHR---------EGQSVYLRAWGDWEHHTLKLTESPEAGLGHIAWRASS 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 695723856  82 KEGLYQILEVLKANQVEIEFEPTLLREGPSMHmmCYEPSGIRVEFYY 128
Cdd:cd09013   73 PEALERRVAALEASGVGIGWIDGDLGQGPAYR--FQSPDGHPMEIYW 117

N-terminal of Bacillus subtilis CatE like protein; Uncharacterized subfamily of VOC superfamily contains Bacillus subtilis CatE and similar proteins. CatE is proposed to function as Catechol-2,3-dioxygenase. 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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856   5 HGVQHVGLAVSNLEESAAFFTDLLGWQEVKRRDDYPAIFVKDGAVMLTLwkTQTEEPIQFNRkNNVGLHHLALQVETKEG 84
Cdd:cd07255    1 TRIGRVTLKVADLERQSAFYQNVIGLSVLKQNASRAYLGVDGKQVLLVL--EAIPDAVLAPR-STTGLYHFAILLPDRKA 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 695723856  85 LYQILEVLKANQVEIEFEPTLLREGPSMHmmcyEPSGIRVEFY 127
Cdd:cd07255   78 LGRALAHLAEHGPLIGAADHGVSEAIYLS----DPEGNGIEIY 116

C-terminal domain of catechol 2,3-dioxygenase; This subfamily contains the C-terminal, catalytic, domain of catechol 2,3-dioxygenase. Catechol 2,3-dioxygenase (2,3-CTD, catechol:oxygen 2,3-oxidoreductase) catalyzes an extradiol cleavage of catechol to form 2-hydroxymuconate semialdehyde with the insertion of two atoms of oxygen. The enzyme is a homotetramer and contains catalytically essential Fe(II) . The reaction proceeds by an ordered bi-unit mechanism. First, catechol binds to the enzyme, this is then followed by the binding of dioxygen to form a tertiary complex, and then the aromatic ring is cleaved to produce 2-hydroxymuconate semialdehyde. Catechol 2,3-dioxygenase belongs to the type I extradiol dioxygenase family. The subunit comprises 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. This subfamily represents the C-terminal domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856   5 HGVQHVGLAVSNLEESAAFFTDLLGWQEVKRrddypaIFVKDGAVMLTLWKTQTEEP--IQF-NRKNNVGLHHLALQVET 81
Cdd:cd07243    5 HRLDHCLLYGERIAETTRFFTDVLGFYLTER------VLDPDGGTRVGIFLSCSNKAhdIAFvGYPEDGKLHHTSFFLES 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 695723856  82 KEGLYQILEVLKANQVEIEFEPTllREGPSMHMMCY--EPSGIRVE------FYYP 129
Cdd:cd07243   79 WEDVLKAGDIISKNDVSIDIGPT--RHGITRGQTIYffDPSGNRNEtfaggyIAYP 132

C-terminal of Bacillus subtilis CatE like protein, a vicinal oxygen chelate subfamily; Uncharacterized subfamily of vicinal oxygen chelate (VOC) superfamily contains Bacillus subtilis CatE and similar proteins. CatE is proposed to function as Catechol-2,3-dioxygenase. 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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856   9 HVGLAVSNLEESAAFFTDLLGWQEVKRRDDypAIFVKDGA----VMLTLWKTQTEEPIQFNRknnVGLHHLALQVETKEG 84
Cdd:cd16359    2 HIHLRVSDLKAASHFYHQVLGFDIKSRRPG--ALFLSAGGyhhhIGLNTWAGRGLPLPPEDA---TGLAYFTIVLPDQEA 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 695723856  85 LYQILEVLKANQVEIEFEPTLLregpsmhmMCYEPSGIRVEF 126
Cdd:cd16359   77 LAAILERLDLAGYDVEALDDGL--------ELTDPWGITVKF 110

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 695723856   9 HVGLAVSNLEESAAFFTDLLGWQEVKRrddypaifvkDGAvmlTLW-KTQTEEP--IQFNRKNNVGLHHLALQVETKEGL 85
Cdd:cd16360    1 YAELGVPDLEKALEFYTDVLGLQVAKR----------DGN---SVYlRGYEDEHhsLVLYEAPEAGLKHFAFEVASEEDL 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 695723856  86 YQILEVLKANQVEIEFEPTLLREGPSMHMMCYEPSGIRVEFY 127
Cdd:cd16360   68 ERAAASLTALGCDVTWGPDGEVPGGGKGFRFQDPSGHLLELF 109

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 695723856   9 HVGLAVSNLEESAAFFTDL----LGWQEVK------------RRDDYPAIFVKDGAVMLTLWKTQTEEPIQFNRK---NN 69
Cdd:cd08353    6 HVGIVVEDLDAAIAFFTELglelEGRMTVEgewadrvvgldgVRVEIAMLRTPDGHGRLELSKFLTPAAIPGHRPapaNA 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 695723856  70 VGLHHLALQVetkEGLYQILEVLKANQVEI-----EFEPTLLregpsmhmMCY--EPSGIRVEF 126
Cdd:cd08353   86 LGLRHVAFAV---DDIDAVVARLRKHGAELvgevvQYEDSYR--------LCYvrGPEGIIVEL 138

fosfomycin resistant protein subfamily FosA; This subfamily family contains FosA, a fosfomycin resistant protein. FosA is a Mn(II) and K(+)-dependent glutathione transferase. Fosfomycin inhibits the enzyme UDP-N-acetylglucosamine-3-enolpyruvyltransferase (MurA), which catalyzes the first committed step in bacterial cell wall biosynthesis. FosA, catalyzes the addition of glutathione to the antibiotic fosfomycin, (1R,2S)-epoxypropylphosphonic acid, making it inactive. FosA is a Mn(II) dependent enzyme. It is evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                         10        20
                 ....*....|....*....|....
gi 695723856   6 GVQHVGLAVSNLEESAAFFTDLLG 29
Cdd:cd07244    1 GINHITLAVSDLERSLAFYVDLLG 24

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 695723856   3 LTHgVQHVGLAVSNLEESAAFFTDLLGWQEVkRRDDYPAIFVKDGAVMLTLWKTQTEEPiqfnrknnvGLHHLALQVETK 82
Cdd:cd08362    1 VTH-LRYVALGVPDLAAEREFYTEVWGLEEV-AEDDDVVYLRAEGSEHHVLRLRQSDEN---------RLDLIAFAAATR 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 695723856  83 EGLYQILEVLKANQVEIEFEPTLL-REGPSMHMMCYEPSGIRVEF 126
Cdd:cd08362   70 ADVDALAARLAAAGVRILSEPGPLdDPGGGYGFRFFDPDGRTIEV 114

C-terminal, catalytic domain of BphC_JF8, (2,3-dihydroxybiphenyl 1,2-dioxygenase); 2,3-dihydroxybiphenyl 1,2-dioxygenase (BphC) catalyzes the extradiol ring cleavage reaction of 2,3-dihydroxybiphenyl, a key step in the polychlorinated biphenyls (PCBs) degradation pathway (bph pathway). BphC belongs to the type I extradiol dioxygenase family, which requires a metal ion in the active site in its catalytic mechanism. Polychlorinated biphenyl degrading bacteria demonstrate a multiplicity of BphCs. This subfamily of BphC is represented by the enzyme purified from the thermophilic biphenyl and naphthalene degrader, Bacillus sp. JF8. The members in this family of BphC enzymes may use either Mn(II) or Fe(II) as cofactors. The enzyme purified from Bacillus sp. JF8 is Mn(II)-dependent, however, the enzyme from Rhodococcus jostii RHAI has Fe(II) bound to it. BphC_JF8 is thermostable and its optimum activity is at 85 degrees C. The enzymes in this family have an internal duplication. This family represents the C-terminal repeat.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856   9 HVGLAVSNLEESAAFFTDLLGWQEVKRrddypaiFVKDGAVMLTLWKTQTEE--PIQFNRKNNVG---LHHLALQVETKE 83
Cdd:cd09014    9 HLNLLASDVTANRQFMSDTLGFRLREQ-------IRDNNGGEAGAWMSVSSLvhDVAVMRDGKGEpgrLHHLAYWYGTPE 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 695723856  84 GLYQILEVLKANQVEIEFeptllreGPSMH-------MMCYEPSGIRVEFY 127
Cdd:cd09014   82 DLLRAADIFREHGIQIEA-------GPGKHgisqaffLYVYEPGGNRVELF 125

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 695723856   9 HVGLAVSNLEESAAFFTDLLGWQEVKRRDD 38
Cdd:cd16357    1 KVSLAVSDLEKSIDYWSDLLGMKVFEKSEK 30

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 695723856   9 HVGLAVSNLEESAAFFTDLLGWQEVKRRDDYPAIfvKDGAVMLTLWktQTEEPIQFNRKNNV-GLHHLALQVETkeGLYQ 87
Cdd:cd07253    6 HLVLTVKDIERTIDFYTKVLGMTVVTFKEGRKAL--RFGNQKINLH--QKGKEFEPKASAPTpGSADLCFITET--PIDE 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 695723856  88 ILEVLKANQVEIEfEPTLLR---EGPSMHMMCYEPSG--IRVEFY 127
Cdd:cd07253   80 VLEHLEACGVTIE-EGPVKRtgaLGPILSIYFRDPDGnlIELSNY 123

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 695723856  12 LAVSNLEESAAFFTDlLGWQEVKRRDDyPAIFVKDGAVMLTLW-KTQTEEPIQFN-RKNNVGLHHLALQVETKEGLYQIL 89
Cdd:cd07251    4 LGVRDLERSARFYEA-LGWKPNLDPND-GVVFFQLGGTVLALYpRDALAEDAGVSvTGAGFSGVTLAHNVRSREEVDQLL 81

                         90
                 ....*....|....*
gi 695723856  90 EVLKANQVEIEFEPT 104
Cdd:cd07251   82 AKAVAAGGKILKPPQ 96

fosfomycin resistant protein subfamily FosX; This subfamily family contains FosX, a fosfomycin resistant protein. FosX is a Mn(II)-dependent fosfomycin-specific epoxide hydrolase. Fosfomycin inhibits the enzyme UDP-Nacetylglucosamine-3-enolpyruvyltransferase (MurA), which catalyzes the first committed step in bacterial cell wall biosynthesis. FosX catalyzes the addition of a water molecule to the C1 position of the antibiotic with inversion of the configuration at C1 in the presence of Mn(II). The hydrated fosfomycin loses the inhibition activity. FosX is evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695723856   6 GVQHVGLAVSNLEESAAFFTDLLGWQEVKRRDD-----YPAIFVKDGAVMLTLWKTqteEPIQfNRknnvGLHHLALQVE 80
Cdd:cd08364    3 GISHITFIVKDLDRTAAFLTEIFGAEEVYDSGAetfslSPEKFFLIGGLWIAIMEG---EPLL-ER----SYNHIAFKVS 74

                         90       100
                 ....*....|....*....|
gi 695723856  81 TKEgLYQILEVLKANQVEIE 100
Cdd:cd08364   75 EGD-LDEYRARIKKLGLEIR 93