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 447068013   8 HVGLMVANLEASISFYEEVVGLQLLKRMGHPnpdlKLAFLGVEEskETILELIEGYNSSLPAEGKVHHICFKVDSLEDEI 87
Cdd:cd06587    1 HVALRVPDLDASVAFYEEVLGFEVVSRNEGG----GFAFLRLGP--GLRLALLEGPEPERPGGGGLFHLAFEVDDVDEVD 74

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 447068013  88 ERLKKHAVTFLLGDEIETLPDGTRYIFFAGPDGEWIEF 125
Cdd:cd06587   75 ERLREAGAEGELVAPPVDDPWGGRSFYFRDPDGNLIEF 112

lactoylglutathione lyase; Lactoylglutathione lyase is also known as aldoketomutase and glyoxalase I. Glyoxylase I is a homodimer in many species. In some eukaryotes, including yeasts and plants, the orthologous protein carries a tandem duplication, is twice as long, and hits this model twice. [Central intermediary metabolism, Amino sugars, Energy metabolism, Other]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013    4 RRIEHVGLMVANLEASISFYEEVVGLQLLKRMGHPNPDLKLAFLGVE-ESKETILELIEGYNSSLPAEGKVH-HICFKVD 81
Cdd:TIGR00068  16 RRLLHTMLRVGDLDKSLDFYTEVLGMKLLRKRDFPEMKFSLAFLGYGdETSAAVIELTHNWGTEKYDLGNGFgHIAIGVD 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 447068013   82 SLEDEIERLKKHAVTFLlgDEIETLPDGTRYI-FFAGPDGEWIEFFET 128
Cdd:TIGR00068  96 DVYKACERVRALGGNVV--REPGPVKGGTTVIaFVEDPDGYKIELIQR 141

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 447068013   8 HVGLMVANLEASISFYEEVVGLQLLKRMGHPnpdlKLAFLGVEEskETILELIEGYNSSLPAEGKVHHICFKVDSLEDEI 87
Cdd:cd06587    1 HVALRVPDLDASVAFYEEVLGFEVVSRNEGG----GFAFLRLGP--GLRLALLEGPEPERPGGGGLFHLAFEVDDVDEVD 74

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 447068013  88 ERLKKHAVTFLLGDEIETLPDGTRYIFFAGPDGEWIEF 125
Cdd:cd06587   75 ERLREAGAEGELVAPPVDDPWGGRSFYFRDPDGNLIEF 112

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 447068013   6 IEHVGLMVANLEASISFYEEVVGLQLLKRMGHPNPDLKLAFLGVEESKetiLELIE--GYNSSL------PAEGkVHHIC 77
Cdd:cd07249    1 LDHIGIAVPDLDEALKFYEDVLGVKVSEPEELEEQGVRVAFLELGNTQ---IELLEplGEDSPIakfldkKGGG-LHHIA 76

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 447068013  78 FKVDSLEDEIERLKKHAVTfLLGDEIETLPDGTRYIFF 115
Cdd:cd07249   77 FEVDDIDAAVEELKAQGVR-LLSEGPRIGAHGKRVAFL 113

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013   3 VRRIEHVGLMVANLEASISFYEEVVGLQLLKRMGHpnpdlkLAFLGVEESkETILELIEGYN-SSLPAEGKVHHICFKVD 81
Cdd:COG2514    1 ITRLGHVTLRVRDLERSAAFYTDVLGLEVVEREGG------RVYLRADGG-EHLLVLEEAPGaPPRPGAAGLDHVAFRVP 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 447068013  82 S---LEDEIERLKKHAVTFllgdEIETLPDGTRYIFFAGPDGEWIEFF 126
Cdd:COG2514   74 SradLDAALARLAAAGVPV----EGAVDHGVGESLYFRDPDGNLIELY 117

Glyoxalase I that uses Ni(++) as cofactor; This family includes Escherichia coil and other prokaryotic glyoxalase I that uses nickel as cofactor. Glyoxalase I (also known as lactoylglutathione lyase; EC 4.4.1.5) is part of the glyoxalase system, a two-step system for detoxifying methylglyoxal, a side product of glycolysis. This system is responsible for the conversion of reactive, acyclic alpha-oxoaldehydes into the corresponding alpha-hydroxyacids and involves 2 enzymes, glyoxalase I and II. Glyoxalase I catalyses an intramolecular redox reaction of the hemithioacetal (formed from methylglyoxal and glutathione) to form the thioester, S-D-lactoylglutathione. This reaction involves the transfer of two hydrogen atoms from C1 to C2 of the methylglyoxal, and proceeds via an ene-diol intermediate. Glyoxalase I has a requirement for bound metal ions for catalysis. Eukaryotic glyoxalase I prefers the divalent cation zinc as cofactor, whereas Escherichia coil and other prokaryotic glyoxalase I uses nickel. However, eukaryotic Trypanosomatid parasites also use nickel as a cofactor, which could possibly be explained by acquiring their GLOI gene by horizontal gene transfer. Human glyoxalase I is a two-domain enzyme and it has the structure of a domain-swapped dimer with two active sites located at the dimer interface. In yeast, in various plants, insects and Plasmodia, glyoxalase I is four-domain, possibly the result of a further gene duplication and an additional gene fusing event.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013   8 HVGLMVANLEASISFYEEVVGLQLLKRMGHPNPDLKLAFLGV-EESKETILELIEGYNSSLPAEGKVH-HICFKVDSLED 85
Cdd:cd16358    3 HTMLRVGDLDRSIKFYTEVLGMKLLRKRDYPEGKYTLAFVGYgDEDENTVLELTYNWGVDKYDLGTAYgHIAIGVEDVYE 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 447068013  86 EIERLKKHAVTFLlgDEIETLPDGTRYI-FFAGPDGEWIEF 125
Cdd:cd16358   83 TCERIRKKGGKVT--REPGPMKGGTTVIaFVEDPDGYKIEL 121

Lactoylglutathione lyase-related enzyme, vicinal oxygen chelate (VOC) family [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013   2 PVRRIEHVGLMVANLEASISFYEEVVGLQLLKRMGHPNPdlklaFLGVEESKETILELIEGynSSLPAEGKVHhICFKVD 81
Cdd:COG3324    1 MPGTIVWVELPVDDLERAKAFYEEVFGWTFEDDAGPGGD-----YAEFDTDGGQVGGLMPG--AEEPGGPGWL-LYFAVD 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 447068013  82 SLEDEIERLKKHAVTFLlgDEIETLPDGTRYIFFAGPDGEWIEFFE 127
Cdd:COG3324   73 DLDAAVARVEAAGGTVL--RPPTDIPPWGRFAVFRDPEGNRFGLWQ 116

4-hydroxyphenylpyruvate dioxygenase and related hemolysins [Amino acid transport and metabolism, General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013   1 MPVRRIEHVGLMVA--NLEASISFYEEVVGLQLLKR--------------MGHPNPDLKLAFLGVEESKETILELIEGYN 64
Cdd:COG3185  142 AGLTRIDHIGIAVPrgDLDEWVLFYEDVLGFEEIREediedpyqgvrsavLQSPDGKVRIPLNEPTSPDSQIAEFLEKYR 221

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 447068013  65 sslpAEGkVHHICFKVDSLEDEIERLKKHAVTFLlgDEIETLPDG--TRYiffaGPDGEWIEF 125
Cdd:COG3185  222 ----GEG-IQHIAFATDDIEATVAALRARGVRFL--DIPDNYYDDlePRV----GAHGEDVAF 273

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013    8 HVGLMVANLEASISFYEEVVGLQLL--KRMGHPNPDLKLAFLGVEESKetiLELIE--GYNSSL-PAEGKVHHICFKVDS 82
Cdd:pfam13669   2 HVGIAVPDLDRALALWGALLGLGPEgdYRSEPQNVDLAFALLGDGPVE---VELIQplDGDSPLaRHGPGLHHLAYWVDD 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 447068013   83 LEDEIERLKKHAVTFLLGDeIETLPDGTRYIF 114
Cdd:pfam13669  79 LDAAVARLLDQGYRVAPKG-PRAGAAGRRVAF 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 447068013   3 VRRIEHVGLMVANLEASISFYEEvVGLQLLKRM-----------GHPNPDLKLAFLGVEESkETILEL--------IEGY 63
Cdd:cd08353    1 IKRMDHVGIVVEDLDAAIAFFTE-LGLELEGRMtvegewadrvvGLDGVRVEIAMLRTPDG-HGRLELskfltpaaIPGH 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 447068013  64 NSSLPAEGKVHHICFKVDSLEDEIERLKKHAVTFLlgDEIETLPDGTRYIFFAGPDGEWIEFFE 127
Cdd:cd08353   79 RPAPANALGLRHVAFAVDDIDAVVARLRKHGAELV--GEVVQYEDSYRLCYVRGPEGIIVELAE 140

lactoylglutathione lyase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013  17 EASISFYEEVVGLQLLKRMGHPNPDLKLAFLGVEE----------------SKETILEL-----------IEGYNSSLPA 69
Cdd:PLN02367  87 KASLDFYSRVLGMSLLKRLDFPEMKFSLYFMGYEDtasaptdptertvwtfGQKATIELthnwgtesdpdFKGYHNGNSE 166

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 447068013  70 EGKVHHICFKVDSLEDEIERLKKhavtflLGDEIETLPDGTRY---IFFAGPDGEWIEFFETER 130
Cdd:PLN02367 167 PRGFGHIGITVDDVYKACERFEE------LGVEFVKKPNDGKMkgiAFIKDPDGYWIEIFDLKT 224

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 447068013   5 RIEHVGLMVANLEASISFYEEVVGLQLLKRMGhpnpdlKLAFLGVEESKETI-LELIEGYNSSLPAEGKVHHICFKVDSL 83
Cdd:cd07255    2 RIGRVTLKVADLERQSAFYQNVIGLSVLKQNA------SRAYLGVDGKQVLLvLEAIPDAVLAPRSTTGLYHFAILLPDR 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 447068013  84 EDeIERLKKHavtfLLGDEIETLPDGTRY---IFFAGPDGEWIEFF 126
Cdd:cd07255   76 KA-LGRALAH----LAEHGPLIGAADHGVseaIYLSDPEGNGIEIY 116

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 447068013   6 IEHVGLMVANLEASISFYEEVvgLQLLKRMGHPNP--------DLKLAFLGVEESKETILELIEGYNSSlpaegkvhhIC 77
Cdd:cd07264    1 IAYIVLYVDDFAASLRFYRDV--LGLPPRFLHEEGeyaefdtgETKLALFSRKEMARSGGPDRRGSAFE---------LG 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 447068013  78 FKVDSLEDEIERLKKHAVTFLlgDEIETLPDGTRYIFFAGPDGEWIEFFET 128
Cdd:cd07264   70 FEVDDVEATVEELVERGAEFV--REPANKPWGQTVAYVRDPDGNLIEICEP 118

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 447068013   3 VRRIEHVGLMVANLEASISFYEEVVGLQlLKRMGHPNPdlKLAFlgveesKETILELIE-GYN----SSLPAEGkVHHIC 77
Cdd:cd07253    1 IKRLDHLVLTVKDIERTIDFYTKVLGMT-VVTFKEGRK--ALRF------GNQKINLHQkGKEfepkASAPTPG-SADLC 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 447068013  78 FKVDSLEDE-IERLKKHAVTFLLGDEIETLPDGTRY-IFFAGPDGEWIE 124
Cdd:cd07253   71 FITETPIDEvLEHLEACGVTIEEGPVKRTGALGPILsIYFRDPDGNLIE 119

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 447068013   8 HVGLMVANLEASISFYEEVVGLQLLKRMGHPNPDL-KLAFLgveESKETILELIEGYNsslPAEGKVHHICFKVDS--LE 84
Cdd:cd08345    1 HITLIVRDLEKSTAFLQDIFGAREVYSSGDKTFSLsKEKFF---LLGGLWIALMEGES---LQERSYTHIAFQIQSedFD 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 447068013  85 DEIERLKKHAVTFLLGDEiETLPDGtRYIFFAGPDGEWIEF 125
Cdd:cd08345   75 RYAERLGALGVEMRPPRP-RVEGEG-RSIYFYDPDNHLFEL 113

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 447068013   1 MPVRRIEHVGLMVANLEASISFYEEVVGLQLLKRMGHPNPDLKLAFLGVEESKETILELIEGynssLPAEGKVHHICFKV 80
Cdd:cd09014    2 IPVRRIDHLNLLASDVTANRQFMSDTLGFRLREQIRDNNGGEAGAWMSVSSLVHDVAVMRDG----KGEPGRLHHLAYWY 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 447068013  81 DSLED-----EIERLK---------KHAVT--FLL------GDEIETLPDGTRYIFfaGPDGEWIEFFETER 130
Cdd:cd09014   78 GTPEDllraaDIFREHgiqieagpgKHGISqaFFLyvyepgGNRVELFGGAGYLIF--DPDWEPVEWTEEDL 147

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 447068013  10 GLMVANLEASISFYEEVVGLQLLKRMGHP-----NPDLKLAFLGVEESKETILELIEGYNSSLPAegkvhHICFKVDSLE 84
Cdd:cd08354    5 CLYADDLDAAEAFYEDVLGLKPMLRSGRHaffrlGPQVLLVFDPGATSKDVRTGEVPGHGASGHG-----HFAFAVPTEE 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 447068013  85 -DEIE-RLKKHAVtfllgdEIET---LPDGTRYIFFAGPDGEWIEF 125
Cdd:cd08354   80 lAAWEaRLEAKGV------PIESytqWPEGGKSLYFRDPAGNLVEL 119

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 447068013   8 HVGLMVANLEASISFYEEVVGLQLLKRmghpnpDLKLAFLGVEESKETILELIEGYNSSLpaegkvHHICFKVDSlEDEI 87
Cdd:cd16360    1 YAELGVPDLEKALEFYTDVLGLQVAKR------DGNSVYLRGYEDEHHSLVLYEAPEAGL------KHFAFEVAS-EEDL 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 447068013  88 ERLKKHAVTflLGDEIETLPDGT-----RYIFFAGPDGEWIEFF 126
Cdd:cd16360   68 ERAAASLTA--LGCDVTWGPDGEvpgggKGFRFQDPSGHLLELF 109

lactoylglutathione lyase

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 447068013   4 RRIEHVGLMVANLEASISFYEEVVGLQLLKRMGHPNPDLKLAFLGV-EESKETILELIEGY 63
Cdd:PLN02300  23 RRMLHVVYRVGDLDRTIKFYTECLGMKLLRKRDIPEEKYTNAFLGYgPEDSNFVVELTYNY 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013    6 IEHVGLMVANLEASISFYEEVVGLQLLKRMGHPN----------PDLKLAFLGVEESKETILELIEGYNSSLPAEGKVHH 75
Cdd:pfam13468   1 LDHVVLAVPDLDEAAARFARALGFTVTPGGRHPGmgtanalimfGDGYLELLAVDPEAPAPPRGRWFGLDRLADGEGLLG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 447068013   76 ICFKVDSLEDEIERLKKHAVTF--------------LLGDEIETLPDGTRYIFF 115
Cdd:pfam13468  81 WALRTDDIDAVAARLRAAGVEPgrrvrpdggdlrwrLLFLADGALPAGGLLPFL 134

N-terminal domain of catechol 2,3-dioxygenase; This subfamily contains the N-terminal, non-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 N-terminal domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013   3 VRRIEHVGLMVANLEASISFYEEVVGLQLLKRMGHPNPDLKlaflGVEESKETILELIEGYNSSLpaegkvHHICFKVDS 82
Cdd:cd07265    2 VLRPGHVQLRVLDLEEAIKHYREVLGLVETGRDDQGRVYLK----AWDEYDHHSIILREADTAGL------DFMGFKVLD 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 447068013  83 LEDeIERLKKHAVTFllGDEIETLPDGT-----RYIFFAGPDGEWIEFF 126
Cdd:cd07265   72 DAD-LEQLEARLQAY--GVTVTRIPAGElpgvgRRVRFQLPSGHTMELY 117

N-terminal domain of 3,4-dihydroxyphenylacetate 2,3-dioxygenase (HPCD); This subfamily contains the N-terminal, non-catalytic, domain of HPCD. HPCD catalyses the second step in the degradation of 4-hydroxyphenylacetate to succinate and pyruvate. The aromatic ring of 4-hydroxyphenylacetate is opened by this dioxygenase to yield the 3,4-diol product, 2-hydroxy-5-carboxymethylmuconate semialdehyde. HPCD is a homotetramer and each monomer contains two structurally homologous barrel-shaped domains at the N- and C-terminus. The active-site metal is located in the C-terminal barrel and plays an essential role in the catalytic mechanism. Most extradiol dioxygenases contain Fe(II) in their active site, but HPCD can be activated by either Mn(II) or Fe(II). These enzymes belong to the type I class II family of extradiol dioxygenases. The class III 3,4-dihydroxyphenylacetate 2,3-dioxygenases belong to a different superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447068013   5 RIEHVGLMVANLEASISFYEEVVGLQLLkrmghpNPDLKLAFL-GVEESKETILELIEGynsslpAEGKVHHICFKVDSL 83
Cdd:cd07266    4 RLAHAELVVTDLAASREFYVDTLGLHVT------DEDDNAIYLrGVEEFIHHTLVLRKA------PEAAVGHLGFRVRDE 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 447068013  84 EDeIERLKKHAVTFLLGDEIETLPDGTRYIFFAGPDGEWIEFF-ETER 130
Cdd:cd07266   72 AD-LDKAAAFYKELGLPTEWREEPGQGRTLRVEDPFGFPIEFYlEMDH 118

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 447068013   6 IEHVGLMVANLEASISFYEEVVGLQLLKR 34
Cdd:cd07244    2 INHITLAVSDLERSLAFYVDLLGFKPHVR 30

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 447068013   9 VGLMVANLEASISFYEEVVGLQLLKRMGHpnpdlkLAFLGVEESKETILELIEGYNSSLPAEGKVHH----ICFKVDSLE 84
Cdd:cd08359    5 PVIVTEDVAATAAFYVKHFGFRVIFDSDW------YVSLRRAERHGFELAIMDGQHGAVPAASQTQSsgliINFEVDDAD 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 447068013  85 DEIERLKKHAVTFLLgdEIETLPDGTRYIFFAGPDGEWIE 124
Cdd:cd08359   79 AEYERLTQAGLEFLE--PPRDEPWGQRRFIVRDPNGVLID 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 447068013   5 RIEHVGLMVANLEASISFYEEVVGLQLLKRMGHPNPDLKLAFLGVEESKETILELIEGynsslPAEGKVHHICFKVDSLE 84
Cdd:cd07243    6 RLDHCLLYGERIAETTRFFTDVLGFYLTERVLDPDGGTRVGIFLSCSNKAHDIAFVGY-----PEDGKLHHTSFFLESWE 80