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 446538878   6 WFNLHVQDLEKSAQFYKALGFKINRNPqmLDKMVGIQIGQTTVILIENKHFQNVSQQSL-NTEPNEVMISLGVNTNEEVD 84
Cdd:cd07251    1 LITLGVRDLERSARFYEALGWKPNLDP--NDGVVFFQLGGTVLALYPRDALAEDAGVSVtGAGFSGVTLAHNVRSREEVD 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 446538878  85 QLLNKVKEAGGTVVQEPTVSQ-GFYGAMFKDLDGHHFNFLVC 125
Cdd:cd07251   79 QLLAKAVAAGGKILKPPQEVFwGGYSGYFADPDGHIWEVAYN 120

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 446538878   6 WFNLHVQDLEKSAQFYKALGFKINRNPqmLDKMVGIQIGQTTVILIENKHFQNVSQQSL-NTEPNEVMISLGVNTNEEVD 84
Cdd:cd07251    1 LITLGVRDLERSARFYEALGWKPNLDP--NDGVVFFQLGGTVLALYPRDALAEDAGVSVtGAGFSGVTLAHNVRSREEVD 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 446538878  85 QLLNKVKEAGGTVVQEPTVSQ-GFYGAMFKDLDGHHFNFLVC 125
Cdd:cd07251   79 QLLAKAVAAGGKILKPPQEVFwGGYSGYFADPDGHIWEVAYN 120

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446538878    6 WFNLHVQDLEKSAQFY-KALGFK----INRNPQMLDKMVGIQIGQTTVILIENKhfqnvsqqslNTEPNEVMISLG---- 76
Cdd:pfam00903   4 HVALRVGDLEKSLDFYtDVLGFKlveeTDAGEEGGLRSAFFLAGGRVLELLLNE----------TPPPAAAGFGGHhiaf 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 446538878   77 -VNTNEEVDQLLNKVKEAGGTVVQEPTvsQGFYGAM---FKDLDGH 118
Cdd:pfam00903  74 iAFSVDDVDAAYDRLKAAGVEIVREPG--RHGWGGRysyFRDPDGN 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 446538878   6 WFNLHVQDLEKSAQFYKALGFKINRNPqmLDKMVGIQIGQTTVILIENKHFQNVSQQSL-NTEPNEVMISLGVNTNEEVD 84
Cdd:cd07251    1 LITLGVRDLERSARFYEALGWKPNLDP--NDGVVFFQLGGTVLALYPRDALAEDAGVSVtGAGFSGVTLAHNVRSREEVD 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 446538878  85 QLLNKVKEAGGTVVQEPTVSQ-GFYGAMFKDLDGHHFNFLVC 125
Cdd:cd07251   79 QLLAKAVAAGGKILKPPQEVFwGGYSGYFADPDGHIWEVAYN 120

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 446538878   5 MWF-NLHVQDLEKSAQFYKALGFKinRNPQMLDKMVGIQI--GQTTVILIENKHFQNVSQQSLNTEP---NEVMISLGVN 78
Cdd:cd09012    1 MIFiNLPVTDLEASTAFYEALGFK--KNPQFSDEHASCMVvsDNIFVMLLAHDRFKTFIPEPIAVDAkksTEVLLTLSAK 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 446538878  79 TNEEVDQLLNKVKEAGGTVV-QEPTVSQGF-YGAMFKDLDGH 118
Cdd:cd09012   79 SRQEVDAFVDKAVEAGGKADpYVNGGDEGFmYGRSFEDLDGH 120

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 446538878   9 LHVQDLEKSAQFY-KALGFKINRNPQMLD---KMVGIQIGQTTVILIenkhFQNVSQQSLNTEPNEVMISLGVntnEEVD 84
Cdd:COG0346    8 LRVSDLEASLAFYtDVLGLELVKRTDFGDggfGHAFLRLGDGTELEL----FEAPGAAPAPGGGGLHHLAFRV---DDLD 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 446538878  85 QLLNKVKEAGGTVVQEPTV-SQGFYGAMFKDLDGH 118
Cdd:COG0346   81 AAYARLRAAGVEIEGEPRDrAYGYRSAYFRDPDGN 115

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 446538878   9 LHVQDLEKSAQFYK-ALGFKINRNPQMlDKMVGIQIG----QTTVILIENKHFQNVSQQSLNTEPNEVMISLGVntnEEV 83
Cdd:cd07263    4 LYVDDQDKALDFYVeKLGFEVVEDVPM-GGMRWVTVAppgsPGTSLLLEPKAHPAQMPQSPEAAGGTPGILLAT---DDI 79

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 446538878  84 DQLLNKVKEAGGTVVQEPTvsQGFYG--AMFKDLDGHHF 120
Cdd:cd07263   80 DATYERLTAAGVTFVQEPT--QMGGGrvANFRDPDGNLF 116

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 446538878   7 FNLHVQDLEKSAQFY-KALGFKINRNPQMLDKmVGIQIGQTTVI-LIENKHFQNVSQQSLNTepnevmISLGVNTNEEVD 84
Cdd:cd06587    2 VALRVPDLDASVAFYeEVLGFEVVSRNEGGGF-AFLRLGPGLRLaLLEGPEPERPGGGGLFH------LAFEVDDVDEVD 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 446538878  85 QLLNKVKEAGGTVVQEPTVSQGFYGAMFKDLDGH 118
Cdd:cd06587   75 ERLREAGAEGELVAPPVDDPWGGRSFYFRDPDGN 108

phenazine resistance protein, EhpR; Phenazine resistance protein (EhpR) in Enterobacter agglomerans confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. EhpR is evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446538878   9 LHVQDLEKSAQFYKALgfkinrnpqmLDKMVgIQIGQTTViLIENKHFQNVSQQSLNTEPNEVM-------ISLGVNTNE 81
Cdd:cd07261    4 LYVDNPERSTEFYRFL----------LGKEP-VESSPTFA-SFVLSGGAKLGLWSSEEVEPKVAvtgggaeLSFMVPSGE 71

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 446538878  82 EVDQLLNKVKEAGGTVVQEPTVSQGFYGAMFKDLDGH 118
Cdd:cd07261   72 QVDEVYAEWKAMGIPIIQEPTTMDFGYTFVATDPDGH 108

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 446538878   1 MIQSMwfnLHVQDLEKSAQFY-KALGFKINRNPQMLD-----KMVGIQiGQTTVILIENKHFQNVSQQSLNTEPNEVMIS 74
Cdd:cd16358    1 MLHTM---LRVGDLDRSIKFYtEVLGMKLLRKRDYPEgkytlAFVGYG-DEDENTVLELTYNWGVDKYDLGTAYGHIAIG 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 446538878  75 lgvntNEEVDQLLNKVKEAGGTVVQEPTVSQGFYG--AMFKDLDGHHFNFL 123
Cdd:cd16358   77 -----VEDVYETCERIRKKGGKVTREPGPMKGGTTviAFVEDPDGYKIELI 122

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446538878   8 NLHVQDLEKSAQFY-KALGFK-INRNPQMLdkMVGIQIGQTTVILIENKHFQ-NVSQQSLNTepnevmISLGVNTNEEVD 84
Cdd:COG2514    8 TLRVRDLERSAAFYtDVLGLEvVEREGGRV--YLRADGGEHLLVLEEAPGAPpRPGAAGLDH------VAFRVPSRADLD 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 446538878  85 QLLNKVKEAGGTV--VQEPTVSQGFYgamFKDLDGHHF 120
Cdd:COG2514   80 AALARLAAAGVPVegAVDHGVGESLY---FRDPDGNLI 114

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 446538878   7 FNLHVQDLEKSAQFY-KALGFKINRNPQMLD-KMVGIQIGQTTVI-LIENKHFQNVSQQSLNtePNEVMISLGVntnEEV 83
Cdd:cd07245    4 VALACPDLERARRFYtDVLGLEEVPRPPFLKfGGAWLYLGGGQQIhLVVEQNPSELPRPEHP--GRDRHPSFSV---PDL 78

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 446538878  84 DQLLNKVKEAgGTVVQEPTVSQGFYGAMF-KDLDG 117
Cdd:cd07245   79 DALKQRLKEA-GIPYTESTSPGGGVTQLFfRDPDG 112

Micromonospora sp. TioX and similar proteins; Micromonospora sp. TioX is encoded by a gene of the thiocoraline biosynthetic gene cluster. Thiocoraline is a thiodepsipeptide with potent antitumor activity. TioX may be involved in thiocoraline resistance or secretion. TioX belongs to vicinal oxygen chelate (VOC) superfamily that 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 446538878  65 NTEPNEVMISLGVNTN------EEVDQLLNKVKEAGGTVVQEPTVSQ-GFYGAMFKDLDGHHFNF 122
Cdd:cd08355   56 EARPDRPADAGGHGTQsvyvavADPDAHYERARAAGAEIVMEPTDTDyGSRDYSARDPEGHLWSF 120