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 16129609     2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGPETEEAVIELTYNWGVDKYELGTAYGHIALSVDN 81
Cdd:TIGR00068  17 RLLHTMLRVGDLDKSLDFYTEVLGMKLLRKRDFPEMKFSLAFLGYGDETSAAVIELTHNWGTEKYDLGNGFGHIAIGVDD 96

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 16129609    82 AAEACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYKIELIEEKDAGRGLGN 135
Cdd:TIGR00068  97 VYKACERVRALGGNVVREPGPVKGGTTVIAFVEDPDGYKIELIQRKSTKDGLGN 150

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 16129609     2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGPETEEAVIELTYNWGVDKYELGTAYGHIALSVDN 81
Cdd:TIGR00068  17 RLLHTMLRVGDLDKSLDFYTEVLGMKLLRKRDFPEMKFSLAFLGYGDETSAAVIELTHNWGTEKYDLGNGFGHIAIGVDD 96

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 16129609    82 AAEACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYKIELIEEKDAGRGLGN 135
Cdd:TIGR00068  97 VYKACERVRALGGNVVREPGPVKGGTTVIAFVEDPDGYKIELIQRKSTKDGLGN 150

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 16129609   3 LLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGPETEEAVIELTYNWGVDKYELGTAYGHIALSVDNA 82
Cdd:cd16358   1 MLHTMLRVGDLDRSIKFYTEVLGMKLLRKRDYPEGKYTLAFVGYGDEDENTVLELTYNWGVDKYDLGTAYGHIAIGVEDV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 16129609  83 AEACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYKIELI 124
Cdd:cd16358  81 YETCERIRKKGGKVTREPGPMKGGTTVIAFVEDPDGYKIELI 122

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609     2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKyslAFVGYGPETEEAVIELTYNWGVDKYELGTA---YGHIALS 78
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKLVEETDAGEEG---GLRSAFFLAGGRVLELLLNETPPPAAAGFGghhIAFIAFS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 16129609    79 VDNAAEACEKIRQNGGNVTREAGPVKGGTTVIaFVEDPDGYKIEL 123
Cdd:pfam00903  78 VDDVDAAYDRLKAAGVEIVREPGRHGWGGRYS-YFRDPDGNLIEL 121

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 16129609     2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGPETEEAVIELTYNWGVDKYELGTAYGHIALSVDN 81
Cdd:TIGR00068  17 RLLHTMLRVGDLDKSLDFYTEVLGMKLLRKRDFPEMKFSLAFLGYGDETSAAVIELTHNWGTEKYDLGNGFGHIAIGVDD 96

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 16129609    82 AAEACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYKIELIEEKDAGRGLGN 135
Cdd:TIGR00068  97 VYKACERVRALGGNVVREPGPVKGGTTVIAFVEDPDGYKIELIQRKSTKDGLGN 150

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 16129609   3 LLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGPETEEAVIELTYNWGVDKYELGTAYGHIALSVDNA 82
Cdd:cd16358   1 MLHTMLRVGDLDRSIKFYTEVLGMKLLRKRDYPEGKYTLAFVGYGDEDENTVLELTYNWGVDKYDLGTAYGHIAIGVEDV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 16129609  83 AEACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYKIELI 124
Cdd:cd16358  81 YETCERIRKKGGKVTREPGPMKGGTTVIAFVEDPDGYKIELI 122

lactoylglutathione lyase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609    2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGPETEEAVIELTYNWGVDKYELGTAYGHIALSVDN 81
Cdd:PLN02300 154 PLCQVMLRVGDLDRSIKFYEKAFGMKLLRKRDNPEYKYTIAMMGYGPEDKTTVLELTYNYGVTEYTKGNAYAQIAIGTDD 233

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 16129609   82 AAEACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYKIELIEEKD 128
Cdd:PLN02300 234 VYKTAEAIKLVGGKITREPGPLPGINTKITACLDPDGWKTVFVDNID 280

Catechol 2,3-dioxygenase or related enzyme, vicinal oxygen chelate (VOC) family [Secondary metabolites biosynthesis, transport and catabolism];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609   1 MRLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGpetEEAVIELTYNWGVDKYELGTAYGHIALSVD 80
Cdd:COG0346   1 MGLHHVTLRVSDLEASLAFYTDVLGLELVKRTDFGDGGFGHAFLRLG---DGTELELFEAPGAAPAPGGGGLHHLAFRVD 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 16129609  81 NAAEACEKIRQNGGNVTREAGPVKGGTTViAFVEDPDGYKIELIEEKDA 129
Cdd:COG0346  78 DLDAAYARLRAAGVEIEGEPRDRAYGYRS-AYFRDPDGNLIELVEPPPG 125

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609     2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKyslAFVGYGPETEEAVIELTYNWGVDKYELGTA---YGHIALS 78
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKLVEETDAGEEG---GLRSAFFLAGGRVLELLLNETPPPAAAGFGghhIAFIAFS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 16129609    79 VDNAAEACEKIRQNGGNVTREAGPVKGGTTVIaFVEDPDGYKIEL 123
Cdd:pfam00903  78 VDDVDAAYDRLKAAGVEIVREPGRHGWGGRYS-YFRDPDGNLIEL 121

N-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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609   2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSE---------NPEY--KYSLAFVGYGPETEEAVIELTYNWGVDKYELGT 70
Cdd:cd08358   2 RALHFVFKVGDRNKTIKFYREILGMKVLRHEEfeegckaacNGPYdgKWSKTMVGYGPEDDHFVVELTYNYGIGDYELGN 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 16129609  71 AYGHIALSVDNAAEACEKIRQnggnvtreagPVKGGTTVIAFVEDPDGYKIELIEE 126
Cdd:cd08358  82 DFLGITIHSKQAVSRAKKHNW----------PVTQVGDGVYEVKAPGGYKFYLIDK 127

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609   1 MRLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSEnPEYKYslAFVGYGPETEEAVIEltynwgvDKYELGTAYGHIALSVD 80
Cdd:COG3324   3 GTIVWVELPVDDLERAKAFYEEVFGWTFEDDAG-PGGDY--AEFDTDGGQVGGLMP-------GAEEPGGPGWLLYFAVD 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 16129609  81 NAAEACEKIRQNGGNVTREAGPVKGGTTvIAFVEDPDGYKIELIEEKD 128
Cdd:COG3324  73 DLDAAVARVEAAGGTVLRPPTDIPPWGR-FAVFRDPEGNRFGLWQPAA 119

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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609   7 MLRVGDLQRSIDFYTKVLGMKLLRTSENPeykyslAFVGYGPetEEAVIELtynwgVD---KYELGTAYGHIALSV--DN 81
Cdd:cd16357   3 SLAVSDLEKSIDYWSDLLGMKVFEKSEKS------ALLGYGE--DQAKLEL-----VDipePVDHGTAFGRIAFSCpaDE 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 16129609  82 AAEACEKIRQNGGNVTREagPVK----GGTTV-IAFVEDPDGYKI 121
Cdd:cd16357  70 LPPIEEKVKAAGQTILTP--LVSldtpGKATVqVVILADPDGHEI 112

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 16129609   2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENpeyKYSLAFvgygpetEEAVIEL--TYNWGVDKYELGTA-YGHIALS 78
Cdd:cd07253   3 RLDHLVLTVKDIERTIDFYTKVLGMTVVTFKEG---RKALRF-------GNQKINLhqKGKEFEPKASAPTPgSADLCFI 72

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 16129609  79 VD-NAAEACEKIRQNGgnVTREAGPVK--GGTTVIA--FVEDPDGYKIEL 123
Cdd:cd07253  73 TEtPIDEVLEHLEACG--VTIEEGPVKrtGALGPILsiYFRDPDGNLIEL 120

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 16129609     2 RLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVgygpETEEAVIELTYNWGVD----KYELGTAYG--HI 75
Cdd:TIGR03081   1 RIDHVGIAVPDLEEAAKFYEDVLGAQVSEIEELPEQGVKVVFI----ALGNTKVELLEPLGEDspiaKFLEKNGGGihHI 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 16129609    76 ALSVDNAAEACEKIRQNGGNVTREAGPVKGGTTVIAFV--EDPDGYKIELIE 125
Cdd:TIGR03081  77 AIEVDDIEAALETLKEKGVRLIDEEPRIGAHGKPVAFLhpKSTGGVLIELEQ 128

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 16129609   5 HTMLRVGDLQRSIDFYTKVLGMK---LLRTSENPEYK---YSLAFVgygpETEEAVIELTYNwgvdkyELGTAYGHIALS 78
Cdd:cd07242   4 HVELAVSDLHRSFKWFEWILGLGwkeYDTWSFGPSWKlsgGSLLVV----QQTDEFATPEFD------RARVGLNHLAFH 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 16129609  79 VDNAA---EACEKIRQNGGNVT-REAGPVKGGTT-VIAFVEDPDGYKIELI 124
Cdd:cd07242  74 AESREavdELTEKLAKIGGVRTyGDRHPFAGGPPhYAAFCEDPDGIKLELV 124

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 16129609   5 HTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKYS-LAFVGYGP-----ETEEAVIELTYNwgvdkyelgtaygHIALS 78
Cdd:cd08345   1 HITLIVRDLEKSTAFLQDIFGAREVYSSGDKTFSLSkEKFFLLGGlwialMEGESLQERSYT-------------HIAFQ 67

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 16129609  79 VDNA--AEACEKIRQNGGNVTREAGPVKGGTTVIAFVeDPDGYKIEL 123
Cdd:cd08345  68 IQSEdfDRYAERLGALGVEMRPPRPRVEGEGRSIYFY-DPDNHLFEL 113

uncharacterized subfamily of vicinal oxygen chelate (VOC) family; The vicinal oxygen chelate (VOC) superfamily is composed of structurally related proteins with paired beta.alpha.beta.beta.beta motifs that provide a metal coordination environment with two or three open or readily accessible coordination sites to promote direct electrophilic participation of the metal ion in catalysis. VOC domain is found in a variety of structurally related metalloproteins, including the bleomycin resistance protein, glyoxalase I, and type I ring-cleaving dioxygenases. A bound metal ion is required for protein activities for the members of this superfamily. A variety of metal ions have been found in the catalytic centers of these proteins including Fe(II), Mn(II), Zn(II), Ni(II) and Mg(II). The protein superfamily contains members with or without domain swapping. The proteins of this family share three conserved metal binding amino acids with the type I extradiol dioxygenases, which shows no domain swapping.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609   3 LLHTMLRVGDLQRSIDFYTKVLGMKLLrtsENPEykySLAFVGY----GPETEEAVIELTYNWGVDKYELGTAYGHIALS 78
Cdd:cd07245   1 LDHVALACPDLERARRFYTDVLGLEEV---PRPP---FLKFGGAwlylGGGQQIHLVVEQNPSELPRPEHPGRDRHPSFS 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 16129609  79 VDNAAEACEKIRQNGGNVTREAGPVKGGTTViaFVEDPDGYKIEL 123
Cdd:cd07245  75 VPDLDALKQRLKEAGIPYTESTSPGGGVTQL--FFRDPDGNRLEF 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 16129609   5 HTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYKyslaFVGYGPETEEAVIELTYNWGVD-----KYELGTAYGHIALSV 79
Cdd:cd07263   1 QVMLYVDDQDKALDFYVEKLGFEVVEDVPMGGMR----WVTVAPPGSPGTSLLLEPKAHPaqmpqSPEAAGGTPGILLAT 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 16129609  80 DNAAEACEKIRQNGGNVTREagPVKGGTTVIAFVEDPDGYKIELIE 125
Cdd:cd07263  77 DDIDATYERLTAAGVTFVQE--PTQMGGGRVANFRDPDGNLFALME 120

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 16129609  10 VGDLQRSIDFYTKVLGMKLLRTSENPEYKYSLAFVGYGpeteEAVIEL------TYNWGVDKYELGTAYGHIALSVDNAA 83
Cdd:cd07249   8 VPDLDEALKFYEDVLGVKVSEPEELEEQGVRVAFLELG----NTQIELleplgeDSPIAKFLDKKGGGLHHIAFEVDDID 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 16129609  84 EACEKIRQNGGNVTREAGPVKGGTTVIAFVEDPDGYK--IELIE 125
Cdd:cd07249  84 AAVEELKAQGVRLLSEGPRIGAHGKRVAFLHPKDTGGvlIELVE 127

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 16129609   5 HTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYkyslaFVGYGPETEEAVIeltynwgvdKYELGTAYGHIALSVDN--A 82
Cdd:cd16360   1 YAELGVPDLEKALEFYTDVLGLQVAKRDGNSVY-----LRGYEDEHHSLVL---------YEAPEAGLKHFAFEVASeeD 66

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 16129609  83 AEACEKIRQNGG-NVTR-EAGPVKGGTTVIAFvEDPDGYKIELI 124
Cdd:cd16360  67 LERAAASLTALGcDVTWgPDGEVPGGGKGFRF-QDPSGHLLELF 109

vicinal oxygen chelate (VOC) family protein Bacillus subtilis YwkD and similar proteins; uncharacterized subfamily of vicinal oxygen chelate (VOC) family contains Bacillus subtilis YwkD 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 16129609  12 DLQRSIDFYTKVLGMKLLRTSENPE---YKYSLAFVGYGPET---EEAVIELTYnwgvdkyelGTAYG--HIALSVDNAA 83
Cdd:cd08352  12 DYEKSKDFYVDKLGFEIIREHYRPErndIKLDLALGGYQLELfikPDAPARPSY---------PEALGlrHLAFKVEDVE 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 16129609  84 EACEKIRQNGgnVTREagPVKggTTVI-----AFVEDPDGYKIELIE 125
Cdd:cd08352  83 ATVAELKSLG--IETE--PIR--VDDFtgkkfTFFFDPDGLPLELYE 123

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 16129609   1 MRLLHTMLRVGDLQRSIDFYTKVLGMKLLRTSENPEYkysLAFVGYGP-----ETEEAVIEltyNWGV-----------D 64
Cdd:cd07255   1 TRIGRVTLKVADLERQSAFYQNVIGLSVLKQNASRAY---LGVDGKQVllvleAIPDAVLA---PRSTtglyhfaillpD 74

                        90
                ....*....|..
gi 16129609  65 KYELGTAYGHIA 76
Cdd:cd07255  75 RKALGRALAHLA 86

The single-domain 2,3-dihydroxybiphenyl 1,2-dioxygenases; This subfamily contains Rhodococcus globerulus P6 BphC2-RGP6 and BphC3-RGP6, and similar proteins. BphC catalyzes the extradiol ring cleavage reaction of 2,3-dihydroxybiphenyl, yielding 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid. This is 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. Most type I extradiol dioxygenases are activated by Fe(II). 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. BphC2-RGP6 and BphC3-RGP6 are one-domain dioxygenases, which form hexamers. BphC1-RGP6 has an internal duplication, it is a two-domain dioxygenase which forms octamers, its two domains do not belong to this subfamily.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609   2 RLLHTMLRVGD--LQRSIDFYTKVLGMKLlrTSENPeykySLAFVGYGPETEEAVIELTYNWGVDKYELGTAYG--HIAL 77
Cdd:cd08348   1 KLAHFVLRTNPekFEAMVQWYLDILGARI--VARNA----KGCFLSFDEEHHRIAIFGAPGGAQPPDKRPTRVGlaHIAF 74

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 16129609  78 SVDNAaeacEKIRQNGGNVtREAG-----PVKGGTTVIAFVEDPDGYKIEL 123
Cdd:cd08348  75 TYASL----DDLARNYAQL-KERGikpvwPVNHGVTTSIYYRDPDGNMLEM 120

Toxoflavin Lyase; Toxoflavin lyase (TflA) is metalloenzyme degrading toxoflavin at the presence of oxygen, Mn(II), and dithiothreitol. TflA is structurally homologous to proteins of the vicinal oxygen chelate superfamily. The structure of TflA contains fold that displays a rare rearrangement of the structural modules indicative of domain permutation. Moreover, unlike the 2-His-1-carboxylate facial triad commonly utilized by vicinal oxygen chelate dioxygenases and other dioxygen-activating non-heme Fe(II) enzymes, the metal center in TflA consists of a 1-His-2-carboxylate facial triad. Toxoflavin is an azapteridine that is toxic to various plants, fungi, animals, and bacteria.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16129609   8 LRVGDLQRSIDFYTKVLGMKllrtsenPEYKYSLAFVgygPETEEAVIELTYNwgvDKYELGTAYGHIALSVdNAAEACE 87
Cdd:cd16362   5 LYAPNLERSLAFYTNFLGAQ-------HVHESNDAFT---VLLNVSSIQLVAA---AEGTASSPFYHIAINI-SANHFQE 70

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 16129609  88 --KIRQNGGNVTREAGpvKGGTTVIAFVEDPDGYKIELIE 125
Cdd:cd16362  71 gkAALSGGGELLTEND--EDQNASSCYVEDPSGNLIELIG 108

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 16129609   1 MRLLHTMLRVGDLQRSIDFYTKVLGMK-LLRTSENPEY--------KYS----------LAFVGYGPETEEAVIELTYN- 60
Cdd:cd07265   3 LRPGHVQLRVLDLEEAIKHYREVLGLVeTGRDDQGRVYlkawdeydHHSiilreadtagLDFMGFKVLDDADLEQLEARl 82

                ....*
gi 16129609  61 --WGV 63
Cdd:cd07265  83 qaYGV 87

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
                ....*....|....*....|....*....|
gi 16129609   8 LRVGDLQRSIDFYTKVLGMKLLRTSENPEY 37
Cdd:cd08349   4 LPVRDIDKTLAFYVDVLGFEVDYERPPPGY 33

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
                ....*....|....*....|....*..
gi 16129609   2 RLLHTMLRVGDLQRSIDFYTKVLGMKL 28
Cdd:cd08360   3 RLGHVLLFSPDVDRSVDFYRDLLGLKV 29