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 1240431729  49 RLNHVAVAVPDLEKASSFYRDVLGAQ-----------------------------------------------------V 75
Cdd:TIGR03081   1 RIDHVGIAVPDLEEAAKFYEDVLGAQvseieelpeqgvkvvfialgntkvelleplgedspiakflekngggihhiaieV 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1240431729  76 DNISAAVMDLKKKKIRSLSDEAKIGAHGKPVIFLHPKDCGGVLVELEQ 123
Cdd:TIGR03081  81 DDIEAALETLKEKGVRLIDEEPRIGAHGKPVAFLHPKSTGGVLIELEQ 128

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 1240431729  49 RLNHVAVAVPDLEKASSFYRDVLGAQ-----------------------------------------------------V 75
Cdd:TIGR03081   1 RIDHVGIAVPDLEEAAKFYEDVLGAQvseieelpeqgvkvvfialgntkvelleplgedspiakflekngggihhiaieV 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1240431729  76 DNISAAVMDLKKKKIRSLSDEAKIGAHGKPVIFLHPKDCGGVLVELEQ 123
Cdd:TIGR03081  81 DDIEAALETLKEKGVRLIDEEPRIGAHGKPVAFLHPKSTGGVLIELEQ 128

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1240431729  46 KLGRLNHVAVAVP--DLEKASSFYRDVLGAQ------------------------------------------------- 74
Cdd:COG3185   143 GLTRIDHIGIAVPrgDLDEWVLFYEDVLGFEeireediedpyqgvrsavlqspdgkvriplneptspdsqiaeflekyrg 222

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1240431729  75 ---------VDNISAAVMDLKKKKIRSLSD--------EAKIGAHGKPVIFLHPK------DCGGVLVEL 121
Cdd:COG3185   223 egiqhiafaTDDIEATVAALRARGVRFLDIpdnyyddlEPRVGAHGEDVAFLHPKgilvdrDTGGVLLQI 292

metallothiol transferase FosB;

                          10        20
                  ....*....|....*....|....*....
gi 1240431729  46 KLGRLNHVAVAVPDLEKASSFYRDVLGAQ 74
Cdd:PRK04101    1 MLKGINHICFSVSNLEKSIEFYEKVLGAK 29

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 1240431729  49 RLNHVAVAVPDLEKASSFYRDVLGAQ-----------------------------------------------------V 75
Cdd:TIGR03081   1 RIDHVGIAVPDLEEAAKFYEDVLGAQvseieelpeqgvkvvfialgntkvelleplgedspiakflekngggihhiaieV 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1240431729  76 DNISAAVMDLKKKKIRSLSDEAKIGAHGKPVIFLHPKDCGGVLVELEQ 123
Cdd:TIGR03081  81 DDIEAALETLKEKGVRLIDEEPRIGAHGKPVAFLHPKSTGGVLIELEQ 128

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1240431729  46 KLGRLNHVAVAVP--DLEKASSFYRDVLGAQ------------------------------------------------- 74
Cdd:COG3185   143 GLTRIDHIGIAVPrgDLDEWVLFYEDVLGFEeireediedpyqgvrsavlqspdgkvriplneptspdsqiaeflekyrg 222

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1240431729  75 ---------VDNISAAVMDLKKKKIRSLSD--------EAKIGAHGKPVIFLHPK------DCGGVLVEL 121
Cdd:COG3185   223 egiqhiafaTDDIEATVAALRARGVRFLDIpdnyyddlEPRVGAHGEDVAFLHPKgilvdrDTGGVLLQI 292

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20
                  ....*....|....*....|....*..
gi 1240431729  49 RLNHVAVAVPDLEKASSFYRDVLGAQV 75
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKL 27

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

                          10        20
                  ....*....|....*....|....*..
gi 1240431729  49 RLNHVAVAVPDLEKASSFYRDVLGAQV 75
Cdd:COG2514     3 RLGHVTLRVRDLERSAAFYTDVLGLEV 29

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
                  ....*....|....*....|...
gi 1240431729  50 LNHVAVAVPDLEKASSFYRDVLG 72
Cdd:cd07245     1 LDHVALACPDLERARRFYTDVLG 23

C-terminal domain of 2,3-dihydroxybiphenyl 1,2-dioxygenase; This subfamily contains the C-terminal, catalytic, domain of BphC1-RGP6 and similar proteins. BphC catalyzes the extradiol ring cleavage reaction of 2,3-dihydroxybiphenyl, 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. 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. BphC1-RGP6 has an internal duplication, it is a two-domain dioxygenase which forms octamers, and has Fe(II) at the catalytic site. Its C-terminal repeat is represented in this subfamily. BphC2-RGP6 and BphC3-RGP6 are one-domain dioxygenases, they belong to a different subfamily of the ED_TypeI_classII_C (C-terminal domain of type I, class II extradiol dioxygenases) family.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1240431729  50 LNHVAVAVPDLEKASSFYRDVLGAQvdnisaavmdlkkkkirsLSDEAKIGA---HGKPVIFLH 110
Cdd:cd07237    10 LGHVVLIVPDVDEALAFYTDVLGFR------------------LSDEIRIPLppgVTARLHFLH 55

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
                  ....*....|....*....|....
gi 1240431729  52 HVAVAVPDLEKASSFYRDVLGAQV 75
Cdd:cd16360     1 YAELGVPDLEKALEFYTDVLGLQV 24

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1240431729  49 RLNHVAVAVPDLEKASSFYRDVLGAQVdnisaavmdlkkkkIRSLSDEAKIGAHGKPV 106
Cdd:cd07255     2 RIGRVTLKVADLERQSAFYQNVIGLSV--------------LKQNASRAYLGVDGKQV 45

metallothiol transferase FosB;

                          10        20
                  ....*....|....*....|....*....
gi 1240431729  46 KLGRLNHVAVAVPDLEKASSFYRDVLGAQ 74
Cdd:PRK04101    1 MLKGINHICFSVSNLEKSIEFYEKVLGAK 29

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
                  ....*....|....*....|....
gi 1240431729  50 LNHVAVAVPDLEKASSFYRDVLGA 73
Cdd:cd08363     1 INHITFSVSNLNKSIAFYKDVLDA 24