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 2155057155   3 AEHGTYVEFDTGSTIlalntRESARDITALDIPDTSASNTFEIGFVTENVEAVIKRMREQG-VSIIGEPKVKPWGQTVAY 81
Cdd:pfam12681  28 LDFGENVSFEGGFAI-----QSDFKELIGIDLSIAEQSNNFELYFEVADVDAFLQKIKEIGnIEYLHELKEQPWGQRVFR 102

                          90
                  ....*....|....*.
gi 2155057155  82 IADPDGHYIEICSPME 97
Cdd:pfam12681 103 FYDPDGHIIEIGESME 118

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2155057155   3 AEHGTYVEFDTGSTIlalntRESARDITALDIPDTSASNTFEIGFVTENVEAVIKRMREQG-VSIIGEPKVKPWGQTVAY 81
Cdd:pfam12681  28 LDFGENVSFEGGFAI-----QSDFKELIGIDLSIAEQSNNFELYFEVADVDAFLQKIKEIGnIEYLHELKEQPWGQRVFR 102

                          90
                  ....*....|....*.
gi 2155057155  82 IADPDGHYIEICSPME 97
Cdd:pfam12681 103 FYDPDGHIIEIGESME 118

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2155057155  35 PDTSASNTFEIGFVTENVEAVIKRMREQGVSIIGEPKVKPWGQTVAYIADPDGHYIEICSPME 97
Cdd:COG0346    62 PAPGGGGLHHLAFRVDDLDAAYARLRAAGVEIEGEPRDRAYGYRSAYFRDPDGNLIELVEPPP 124

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2155057155   3 AEHGTYVEFDTGSTIlalntRESARDITALDIPDTSASNTFEIGFVTENVEAVIKRMREQG-VSIIGEPKVKPWGQTVAY 81
Cdd:pfam12681  28 LDFGENVSFEGGFAI-----QSDFKELIGIDLSIAEQSNNFELYFEVADVDAFLQKIKEIGnIEYLHELKEQPWGQRVFR 102

                          90
                  ....*....|....*.
gi 2155057155  82 IADPDGHYIEICSPME 97
Cdd:pfam12681 103 FYDPDGHIIEIGESME 118

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2155057155  35 PDTSASNTFEIGFVTENVEAVIKRMREQGVSIIGEPKVKPWGQTVAYIADPDGHYIEICSPME 97
Cdd:COG0346    62 PAPGGGGLHHLAFRVDDLDAAYARLRAAGVEIEGEPRDRAYGYRSAYFRDPDGNLIELVEPPP 124

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2155057155   8 YVEFDTGSTILALNTRESarditalDIPDTSAsNTFEIGFVTENVEAVIKRMREQGVSIIGEPKVKPWGQTVAYIADPDG 87
Cdd:COG2764    39 HAELRIGGSVLMLSDAPP-------DSPAAEG-NGVSLSLYVDDVDALFARLVAAGATVVMPLQDTFWGDRFGMVRDPFG 110

                  ....*...
gi 2155057155  88 HYIEICSP 95
Cdd:COG2764   111 VLWMINTP 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 2155057155   1 MRAEHGTYVEFDTGSTILALNTRES-ARDITALDipDTSASNTFEIGFVT---ENVEAVIKRMREQGVSIIGEPKVKPWG 76
Cdd:cd07251    24 NLDPNDGVVFFQLGGTVLALYPRDAlAEDAGVSV--TGAGFSGVTLAHNVrsrEEVDQLLAKAVAAGGKILKPPQEVFWG 101

                          90
                  ....*....|....*.
gi 2155057155  77 QTVAYIADPDGHYIEI 92
Cdd:cd07251   102 GYSGYFADPDGHIWEV 117

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 2155057155   2 RAEHGTYVEFDTGS-TILALNTRESARDITALDIpdtsasntFEIGFVTENVEAVIKRMREQGV--SIIGEPKVKPWGQT 78
Cdd:cd06587    27 RNEGGGFAFLRLGPgLRLALLEGPEPERPGGGGL--------FHLAFEVDDVDEVDERLREAGAegELVAPPVDDPWGGR 98

                          90
                  ....*....|....
gi 2155057155  79 VAYIADPDGHYIEI 92
Cdd:cd06587    99 SFYFRDPDGNLIEF 112

Burkholderia Phytofirmans glyoxalase/bleomycin resistance protein/dioxygenase family enzyme and similar proteins; Burkholderia Phytofirmans glyoxalase/bleomycin resistance protein/dioxygenase family enzyme 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 2155057155   1 MRAEHgtYVEFDTGSTILALNTREsARDITALDIPDTSASNTFEIGFVTENVEAV---IKRMREQGVSIIGEPKVKPWGQ 77
Cdd:cd16356    28 IRSPI--FRGLRTGDSCLGFNAPE-AYELLGLPEFSDTPGIRILLTFDVDDVEAVdrlVPRAAALGATLIKPPYDTYYGW 104

                          90
                  ....*....|....*
gi 2155057155  78 TVAYIADPDGHYIEI 92
Cdd:cd16356   105 YQAVLLDPEGNVFRI 119

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
                  ....*....|....*....|....*....|....*....|....*....
gi 2155057155  45 IGFVTENVEAVIKRMREQGVSIIGEPkVKPWGQTVAYIADPDGHYIEIC 93
Cdd:cd07263    72 ILLATDDIDATYERLTAAGVTFVQEP-TQMGGGRVANFRDPDGNLFALM 119

fosfomycin resistant protein subfamily FosB; This subfamily family contains FosB, a fosfomycin resistant protein. FosB is a Mg(2+)-dependent L-cysteine thiol transferase. Fosfomycin inhibits the enzyme UDP-nacetylglucosamine-3-enolpyruvyltransferase (MurA), which catalyzes the first committed step in bacterial cell wall biosynthesis. FosB catalyzes the Mg(II) dependent addition of L-cysteine to the epoxide ring of fosfomycin, (1R,2S)-epoxypropylphosphonic acid, rendering it inactive. FosB is evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2155057155  11 FDTGSTILALNTREsarditalDIPDTSASNTF-EIGFVT--ENVEAVIKRMREQGVSII-GEPKVKPWGQTVaYIADPD 86
Cdd:cd08363    36 FDLNGLWLALNVQE--------DIPRNEISHSYtHIAFSIdeEDLDAFKERLKDNGVNILeGRKRDILEGQSI-YFTDPD 106

                  ....*.
gi 2155057155  87 GHYIEI 92
Cdd:cd08363   107 GHLFEL 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2155057155   2 RAEHGTYVEFDTGSTILALNTRESARditaldiPDTSASNTFEIGFVTEN---VEAVIKRMREQGVSIIGEpkVKPWGQT 78
Cdd:COG2514    32 REGGRVYLRADGGEHLLVLEEAPGAP-------PRPGAAGLDHVAFRVPSradLDAALARLAAAGVPVEGA--VDHGVGE 102

                          90
                  ....*....|....*....
gi 2155057155  79 VAYIADPDGHYIEICSPME 97
Cdd:COG2514   103 SLYFRDPDGNLIELYTDRP 121

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
                  ....*....|....*....|....*....|....*....|....*....
gi 2155057155  45 IGFVTENVEAVIKRMREQGVSIIGEPKVKPWGQTV-AYIADPDGHYIEI 92
Cdd:cd16358    73 IAIGVEDVYETCERIRKKGGKVTREPGPMKGGTTViAFVEDPDGYKIEL 121

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
                  ....*....|....*....|....*....|....*....|....*..
gi 2155057155  49 TENVEAVIKRMREQGVSIIGEPKVKPWGQTVAYIADPDGHYIEICSP 95
Cdd:cd07246    78 VEDVDATFARAVAAGAVVVEPVEDQFWGDRVGKVKDPFGHVWWLATP 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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2155057155  47 FVTE-NVEAVIKRMREQGVSIIgEPKVKPWGQ----TVAYIADPDGHYIEICSP 95
Cdd:cd07253    71 FITEtPIDEVLEHLEACGVTIE-EGPVKRTGAlgpiLSIYFRDPDGNLIELSNY 123

vicinal oxygen chelate (VOC) family protein similar to Streptomyces hygroscopicus ValD protein; This subfamily of vicinal oxygen chelate (VOC) family protein includes Streptomyces hygroscopicus ValD protein and similar proteins. ValD protein functions in validamycin biosynthetic pathway. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2155057155  33 DIPDTSASNTFEIGFVTENVEAVIKRMREQGVSIIGEPKVKPWGQ-----TVAYIADPDGHYIEICS 94
Cdd:cd16361    82 PVPRNSDVGIFHFALQVDDVEAAAERLAAAGGKVLMGPREIPDGGpgkgnRMVYLRDPWGTLIELVS 148

N-terminal domain of Streptomyces griseus SgaA and similar domains; SgaA suppresses the growth disturbances caused by high osmolarity and a high concentration of A-factor, a microbial hormone, during the early growth phase in Streptomyces griseus. A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) controls morphological differentiation and secondary metabolism in Streptomyces griseus. It is a chemical signaling molecule that at a very low concentration acts as a switch for yellow pigment production, aerial mycelium formation, streptomycin production, and streptomycin resistance. The structure and amino acid sequence of SgaA are closely related to a group of antibiotics resistance proteins, including bleomycin resistance protein, mitomycin resistance protein, and fosfomycin resistance proteins. SgaA might also function as a streptomycin resistance protein.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2155057155  45 IGFVTENVEAVIKRMREQGVSIIGEPKVKPWGQTVAYIADPDGHYI 90
Cdd:cd07247    65 IYFAVDDLDAALARVEAAGGKVVVPPTDIPGGGRFAVFADPEGNRF 110

lactoylglutathione lyase

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2155057155  45 IGFVTENVEAVIKRMREQGVSIIGEP---KVKpwgqTVAYIADPDGHYIEI 92
Cdd:PLN02367  173 IGITVDDVYKACERFEELGVEFVKKPndgKMK----GIAFIKDPDGYWIEI 219

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2155057155  45 IGFVTENVEAVIKRMREQGVSIIGE-PKVKPWGQTVAYI--ADPDGHYIEIC 93
Cdd:cd07249    75 IAFEVDDIDAAVEELKAQGVRLLSEgPRIGAHGKRVAFLhpKDTGGVLIELV 126