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 491623272   6 ILHTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDESQGAVIELTYNWGKTEYDLGTAFGHIAIGVDDI 85
Cdd:cd16358    1 MLHTMLRVGDLDRSIKFYTEVLGMKLLRKRDYPEGKYTLAFVGYGDEDENTVLELTYNWGVDKYDLGTAYGHIAIGVEDV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 491623272  86 YATCDAIKAAGGNVTREAGPVKGGTTHIAFVKDPDGYMIELI 127
Cdd:cd16358   81 YETCERIRKKGGKVTREPGPMKGGTTVIAFVEDPDGYKIELI 122

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 491623272   5 RILHTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDesqGAVIELTYNWGKTEYDLGTAFGHIAIGVDD 84
Cdd:COG0346    2 GLHHVTLRVSDLEASLAFYTDVLGLELVKRTDFGDGGFGHAFLRLGD---GTELELFEAPGAAPAPGGGGLHHLAFRVDD 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 491623272  85 IYATCDAIKAAGGNVTREAGPVKGGtTHIAFVKDPDGYMIELIQNKQA 132
Cdd:COG0346   79 LDAAYARLRAAGVEIEGEPRDRAYG-YRSAYFRDPDGNLIELVEPPPG 125

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 491623272   6 ILHTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDESQGAVIELTYNWGKTEYDLGTAFGHIAIGVDDI 85
Cdd:cd16358    1 MLHTMLRVGDLDRSIKFYTEVLGMKLLRKRDYPEGKYTLAFVGYGDEDENTVLELTYNWGVDKYDLGTAYGHIAIGVEDV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 491623272  86 YATCDAIKAAGGNVTREAGPVKGGTTHIAFVKDPDGYMIELI 127
Cdd:cd16358   81 YETCERIRKKGGKVTREPGPMKGGTTVIAFVEDPDGYKIELI 122

lactoylglutathione lyase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491623272   3 NGRILHTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDESQGAVIELTYNWGKTEYDLGTAFGHIAIGV 82
Cdd:PLN02300  22 KRRMLHVVYRVGDLDRTIKFYTECLGMKLLRKRDIPEEKYTNAFLGYGPEDSNFVVELTYNYGVDKYDIGTGFGHFGIAV 101

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 491623272  83 DDIYATCDAIKAAGGNVTREAGPVKGGTTHIAFVKDPDGYMIELIQNK 130
Cdd:PLN02300 102 EDVAKTVELVKAKGGKVTREPGPVKGGKSVIAFVKDPDGYKFELIQRG 149

Glyoxalase I that uses Zn(++) as cofactor; This family includes eukaryotic glyoxalase I that prefers the divalent cation zinc 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 491623272   8 HTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDE-------------SQGAVIELTYNWGK-----TEY 69
Cdd:cd07233    3 HTMLRVKDPKKSLKFYTEVLGMKLLRKKDFPEMKFSLYFLGYEDPkdipkdprtawvfSREGTLELTHNWGTendedPVY 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 491623272  70 DLGTA----FGHIAIGVDDIYATCDAIKAAGgnVTREAGPVKGGTTHIAFVKDPDGYMIELI 127
Cdd:cd07233   83 HNGNSdprgFGHIGIAVDDVYAACERFEELG--VKFKKKPDDGKMKGIAFIKDPDGYWIEIL 142

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491623272    5 RILHTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDesqGAVIELTYNWGKTEYDLGTA---FGHIAIG 81
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKLVEETDAGEEGGLRSAFFLAG---GRVLELLLNETPPPAAAGFGghhIAFIAFS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 491623272   82 VDDIYATCDAIKAAGGNVTREAGPVKGGTThIAFVKDPDGYMIEL 126
Cdd:pfam00903  78 VDDVDAAYDRLKAAGVEIVREPGRHGWGGR-YSYFRDPDGNLIEL 121

lactoylglutathione lyase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491623272   8 HTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDE---------------SQGAVIELTYNWGkTE---- 68
Cdd:PLN02367  78 QTMYRIKDPKASLDFYSRVLGMSLLKRLDFPEMKFSLYFMGYEDTasaptdptertvwtfGQKATIELTHNWG-TEsdpd 156

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 491623272  69 ---YDLGTA----FGHIAIGVDDIYATCDAIKAAGGNVTREagPVKGGTTHIAFVKDPDGYMIEL 126
Cdd:PLN02367 157 fkgYHNGNSeprgFGHIGITVDDVYKACERFEELGVEFVKK--PNDGKMKGIAFIKDPDGYWIEI 219

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 491623272   4 GRILHTMLRVGDLDKSIKFYTEVMGMQLLRTNENKE---------YE--YTLAFVGYGDESQGAVIELTYNWGKTEYDLG 72
Cdd:cd08358    1 RRALHFVFKVGDRNKTIKFYREILGMKVLRHEEFEEgckaacngpYDgkWSKTMVGYGPEDDHFVVELTYNYGIGDYELG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 491623272  73 TAFGHIAIGVDDIYAtcdaikaaggNVTREAGPVKGGTTHIAFVKDPDGY 122
Cdd:cd08358   81 NDFLGITIHSKQAVS----------RAKKHNWPVTQVGDGVYEVKAPGGY 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 491623272  13 VGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDesqgAVIEL------TYNWGKTEYDLGTAFGHIAIGVDDIY 86
Cdd:cd07249    8 VPDLDEALKFYEDVLGVKVSEPEELEEQGVRVAFLELGN----TQIELleplgeDSPIAKFLDKKGGGLHHIAFEVDDID 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 491623272  87 ATCDAIKAAGGNVTREAGPVKGGTTHIAFV--KDPDGYMIELIQ 128
Cdd:cd07249   84 AAVEELKAQGVRLLSEGPRIGAHGKRVAFLhpKDTGGVLIELVE 127

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 491623272  10 MLRVGDLDKSIKFYTEVMGMQLLRTNENKeyeytlAFVGYGDEsqGAVIELTYNWGKTeyDLGTAFGHIAIGV--DDIYA 87
Cdd:cd16357    3 SLAVSDLEKSIDYWSDLLGMKVFEKSEKS------ALLGYGED--QAKLELVDIPEPV--DHGTAFGRIAFSCpaDELPP 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 491623272  88 TCDAIKAAGGNV--------TreagPVKgGTTHIAFVKDPDGYMI 124
Cdd:cd16357   73 IEEKVKAAGQTIltplvsldT----PGK-ATVQVVILADPDGHEI 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 491623272  11 LRVGDLDKSIKFYTEvMGMQLLRTNENKeyeytlaFVGYgdESQGAVIELtYNWGKTEYDLGTA-----FGHIAIG---- 81
Cdd:cd07251    4 LGVRDLERSARFYEA-LGWKPNLDPNDG-------VVFF--QLGGTVLAL-YPRDALAEDAGVSvtgagFSGVTLAhnvr 72

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 491623272  82 ----VDDIYATcdaIKAAGGNVTREAGPVKGGTTHiAFVKDPDGYMIELIQN 129
Cdd:cd07251   73 sreeVDQLLAK---AVAAGGKILKPPQEVFWGGYS-GYFADPDGHIWEVAYN 120

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491623272   7 LHTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGdesqGAVIELTYNWGKTEYDLGTAFgHIAIGVDDIY 86
Cdd:COG2764    2 VTPYLVVDDAEEALEFYEDVFGFEVVFRMTDPDGKIMHAELRIG----GSVLMLSDAPPDSPAAEGNGV-SLSLYVDDVD 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 491623272  87 ATCDAIKAAGGNVTREAGPVKGGTTHiAFVKDPDGYMIELIQ 128
Cdd:COG2764   77 ALFARLVAAGATVVMPLQDTFWGDRF-GMVRDPFGVLWMINT 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 491623272   6 ILHTMLRVGDLDKSIKFYTEVMGmqllrtnenkEYEYTLAF-----VGYGDESQGAVieltynWGKTEYDLGTA----FG 76
Cdd:cd07262    1 ISHVTIGVNDLERSRAFYDAALA----------PLGYKRGFedggrVGYGLEGGPDF------WVTEPFDGEPAtagnGT 64

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 491623272  77 HIAI------GVDDIYATcdAIkAAGGNVTREAG--PVKGGTTHIAFVKDPDGYMIE 125
Cdd:cd07262   65 HVAFaapsraAVDAFHAA--AL-AAGGTDNGAPGlrPHYHPGYYAAYVRDPDGNKIE 118

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 491623272   8 HTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYE-YTLA-------FVGYGDESQGAVIEltynwGKTEYDLGTAFghIA 79
Cdd:cd07263    1 QVMLYVDDQDKALDFYVEKLGFEVVEDVPMGGMRwVTVAppgspgtSLLLEPKAHPAQMP-----QSPEAAGGTPG--IL 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 491623272  80 IGVDDIYATCDAIKAAGGNVTREagPVKGGTTHIAFVKDPDGYMIELIQ 128
Cdd:cd07263   74 LATDDIDATYERLTAAGVTFVQE--PTQMGGGRVANFRDPDGNLFALME 120

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 491623272   13 VGDLDKSIKFYTEVMGMQLLRTNENKEYEYTLAFVGYGDESqgAVIELTYNWGKTEY--DLGTAFGHIAIGVDDIYATCD 90
Cdd:pfam13669   7 VPDLDRALALWGALLGLGPEGDYRSEPQNVDLAFALLGDGP--VEVELIQPLDGDSPlaRHGPGLHHLAYWVDDLDAAVA 84

                          90       100
                  ....*....|....*....|....*
gi 491623272   91 AIKAAGGNVTREAGPVKGGTTHIAF 115
Cdd:pfam13669  85 RLLDQGYRVAPKGPRAGAAGRRVAF 109

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 491623272   8 HTMLRVGDLDKSIKFYTEVMGmqllrtNENKEYEYTLAFVGY-GDESQGAVIELTYNWGKTEYD-LGTAFGHIAIG---- 81
Cdd:cd07242    4 HVELAVSDLHRSFKWFEWILG------LGWKEYDTWSFGPSWkLSGGSLLVVQQTDEFATPEFDrARVGLNHLAFHaesr 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 491623272  82 --VDDIYATcdaIKAAGGNVT-REAGPVKGGTTH-IAFVKDPDGYMIELI 127
Cdd:cd07242   78 eaVDELTEK---LAKIGGVRTyGDRHPFAGGPPHyAAFCEDPDGIKLELV 124

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 491623272   5 RILHTMLRVGDLDKSIKFYTEVMGMQLLRTNENKeyeYTLAFvgygdesqGAVIeltYNWGKTEYDLGTAFGHIAIGVDD 84
Cdd:cd07253    3 RLDHLVLTVKDIERTIDFYTKVLGMTVVTFKEGR---KALRF--------GNQK---INLHQKGKEFEPKASAPTPGSAD 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 491623272  85 I-YATCDAIKA-----AGGNVTREAGPVK-----GGTTHIaFVKDPDGYMIEL 126
Cdd:cd07253   69 LcFITETPIDEvlehlEACGVTIEEGPVKrtgalGPILSI-YFRDPDGNLIEL 120

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 491623272  11 LRVGDLDKSIKFYTEVMGMQLLRTNENKEYeytlaFVGYGDESQgaVIELTynwgkteYDLGTAFGHIAIGVD---DIYA 87
Cdd:cd08362    9 LGVPDLAAEREFYTEVWGLEEVAEDDDVVY-----LRAEGSEHH--VLRLR-------QSDENRLDLIAFAAAtraDVDA 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 491623272  88 TCDAIKAAGGNVTREAGPVK--GGTTHIAFVkDPDGYMIELI 127
Cdd:cd08362   75 LAARLAAAGVRILSEPGPLDdpGGGYGFRFF-DPDGRTIEVS 115

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
                 ....*....|....*....|....*....|....*..
gi 491623272   5 RILHTMLRVGDLDKSIKFYTEVMGMQ-LLRTNENKEY 40
Cdd:cd07265    4 RPGHVQLRVLDLEEAIKHYREVLGLVeTGRDDQGRVY 40

C-terminal domain of 3,4-dihydroxyphenylacetate 2,3-dioxygenase (HPCD); This subfamily contains the C-terminal, 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 491623272   5 RILHTMLRVGDLDKSIKFYtEVMGMQLLRTNENKEYEYTLAFVgygdESQGAVIELTYNWGKteydlGTAFGHIAIGVDD 84
Cdd:cd07256    3 RIDHFNQRVPDVDAGLRYY-EDLGFRVSEYTEDDDGETWAAWM----HRKGGVHDTALTNGN-----GPRLHHVAFWVPE 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 491623272  85 ---IYATCDAIKAAGGNVTREAGPVKGGTTHIAF--VKDPDGYMIEL 126
Cdd:cd07256   73 phnIIQTCDLMAAARYSDRIERGPGRHGVSNAFFlyILDPDGHRIEI 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 491623272   8 HTMLRVGDLDKSIKFYTEVMGMQLLRTNENKEYEYT-LAFVGYGD----ESQG-AVIELTYNwgkteydlgtafgHIAIG 81
Cdd:cd08345    1 HITLIVRDLEKSTAFLQDIFGAREVYSSGDKTFSLSkEKFFLLGGlwiaLMEGeSLQERSYT-------------HIAFQ 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 491623272  82 VD----DIYAtcDAIKAAGGNVTREAGPVKGGTTHIAFVkDPDGYMIEL 126
Cdd:cd08345   68 IQsedfDRYA--ERLGALGVEMRPPRPRVEGEGRSIYFY-DPDNHLFEL 113