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 1125492104   4 VDHLGIAVKSIAQARRFYEQ-LGMKVMDEEVVEHEKLRAAMVPVGESRFELLEGTSDDSVIAKFIAKRGEGLHHVAVHVN 82
Cdd:cd07249     1 LDHIGIAVPDLDEALKFYEDvLGVKVSEPEELEEQGVRVAFLELGNTQIELLEPLGEDSPIAKFLDKKGGGLHHIAFEVD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1125492104  83 DISATFEELKRKGVRLISDEIKVGAGGHLYIFVHPSATGGVLLELCQ 129
Cdd:cd07249    81 DIDAAVEELKAQGVRLLSEGPRIGAHGKRVAFLHPKDTGGVLIELVE 127

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1125492104   5 DHLGIAVKSIAQARRFYE-QLGMKVMDEEVVEHEKLRAAMVPVGESRF--ELLEGTSDDSviakFIAKRGEGLHHVAVHV 81
Cdd:pfam13669   1 HHVGIAVPDLDRALALWGaLLGLGPEGDYRSEPQNVDLAFALLGDGPVevELIQPLDGDS----PLARHGPGLHHLAYWV 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1125492104  82 NDISATFEELKRKGVRLISDEIKVGAGGHLYIF 114
Cdd:pfam13669  77 DDLDAAVARLLDQGYRVAPKGPRAGAAGRRVAF 109

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 1125492104   4 VDHLGIAVKSIAQARRFYEQ-LGMKVMDEEVVEHEKLRAAMVPVGESRFELLEGTSDDSVIAKFIAKRGEGLHHVAVHVN 82
Cdd:cd07249     1 LDHIGIAVPDLDEALKFYEDvLGVKVSEPEELEEQGVRVAFLELGNTQIELLEPLGEDSPIAKFLDKKGGGLHHIAFEVD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1125492104  83 DISATFEELKRKGVRLISDEIKVGAGGHLYIFVHPSATGGVLLELCQ 129
Cdd:cd07249    81 DIDAAVEELKAQGVRLLSEGPRIGAHGKRVAFLHPKDTGGVLIELVE 127

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 1125492104   3 KVDHLGIAVKSIAQARRFYEQ-LGMKVMDEEVVEHEKLRAAMVPVGE-SRFELLEGTSDDSviakfiAKRGEGLHHVAVH 80
Cdd:COG0346     2 GLHHVTLRVSDLEASLAFYTDvLGLELVKRTDFGDGGFGHAFLRLGDgTELELFEAPGAAP------APGGGGLHHLAFR 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1125492104  81 VNDISATFEELKRKGVRlISDEIKVGAGGHLYIFVH-PSatgGVLLELCQDA 131
Cdd:COG0346    76 VDDLDAAYARLRAAGVE-IEGEPRDRAYGYRSAYFRdPD---GNLIELVEPP 123

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1125492104   3 KVDHLGIAVKSIAQARRFYEQ-LGMKVMDEEV-VEHEKLRAAMVPVGESRFELLEGTSDDSVIAKFIakrGEGLHHVAVH 80
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDvLGFKLVEETDaGEEGGLRSAFFLAGGRVLELLLNETPPPAAAGFG---GHHIAFIAFS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1125492104  81 VNDISATFEELKRKGVRlISDEIKVGAGGHLYIFVhpSATGGVLLEL 127
Cdd:pfam00903  78 VDDVDAAYDRLKAAGVE-IVREPGRHGWGGRYSYF--RDPDGNLIEL 121

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1125492104   1 MFKVDHLGIAVKSIAQARRFYEQ-LGMKVmdeEVVEHEKLRAAMVPVGESRfellegtsdDSVIAKFIAKRGEGLHHVAV 79
Cdd:COG3324     2 PGTIVWVELPVDDLERAKAFYEEvFGWTF---EDDAGPGGDYAEFDTDGGQ---------VGGLMPGAEEPGGPGWLLYF 69

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1125492104  80 HVNDISATFEELKRKGVRLISDEIKVGAGGHLYIFVHPSatgGVLLELCQDA 131
Cdd:COG3324    70 AVDDLDAAVARVEAAGGTVLRPPTDIPPWGRFAVFRDPE---GNRFGLWQPA 118

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 1125492104   6 HLGIAVKSIAQARRFYEQ-LGMKVmdeeVVEHEKLRAAMVPVGE-SRFELLEGTSDDSviakfiaKRGEGLHHVAVHVND 83
Cdd:cd06587     1 HVALRVPDLDASVAFYEEvLGFEV----VSRNEGGGFAFLRLGPgLRLALLEGPEPER-------PGGGGLFHLAFEVDD 69

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1125492104  84 ISATFEELKRKGVR-LISDEIKVGAGGHLYIFVHPSatGGVLLEL 127
Cdd:cd06587    70 VDEVDERLREAGAEgELVAPPVDDPWGGRSFYFRDP--DGNLIEF 112

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1125492104   3 KVDHLGIAVKSIAQARRFYEQ-LGMKV-MDEEVVEH-----EKLRAAMVPVGESRFEL-LEGTSDDSVIAKFIAKRGE-- 72
Cdd:cd16361     1 GVNHVGITVPDLDAAVEFYTDvLGAEVvYRSTPLAEgdrggGEMRAAGFVPGFARARIaMLRLGPGPGIELFEYKGPEqr 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1125492104  73 ---------GLHHVAVHVNDISATFEELKRKGVRLISD--EIKVGAGGHLYIFVHPSATGGVLLEL 127
Cdd:cd16361    81 apvprnsdvGIFHFALQVDDVEAAAERLAAAGGKVLMGprEIPDGGPGKGNRMVYLRDPWGTLIEL 146

N-terminal domain of 4-hydroxyphenylpyruvate dioxygenase (HPPD) and hydroxymandelate Synthase (HmaS); HppD and HmaS are non-heme iron-dependent dioxygenases, which modify a common substrate, 4-hydroxyphenylpyruvate (HPP), but yield different products. HPPD catalyzes the second reaction in tyrosine catabolism, the conversion of HPP to homogentisate (2,5-dihydroxyphenylacetic acid, HG). HmaS converts HPP to 4-hydroxymandelate, a committed step in the formation of hydroxyphenylglycerine, a structural component of nonproteinogenic macrocyclic peptide antibiotics, such as vancomycin. If the emphasis is on catalytic chemistry, HPPD and HmaS are classified as members of a large family of alpha-keto acid dependent mononuclear non-heme iron oxygenases most of which require Fe(II), molecular oxygen, and an alpha-keto acid (typically alpha-ketoglutarate) to either oxygenate or oxidize a third substrate. Both enzymes are exceptions in that they require two, instead of three, substrates, do not use alpha-ketoglutarate, and incorporate both atoms of dioxygen into the aromatic product. Both HPPD and HmaS exhibit duplicate beta barrel topology in their N- and C-terminal domains which share sequence similarity, suggestive of a gene duplication. Each protein has only one catalytic site located in at the C-terminal domain. This HPPD_N_like domain represents the N-terminal domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1125492104   4 VDHLGIAVKSIAQARRFYEQ-LGMKVMDEEVVEHEKLRAAMVPVGESRFELLEGTSDDSVIAKFIAKRGEGLHHVAVHVN 82
Cdd:cd08342     1 FDHVEFYVGNAKQAASYYSTgLGFEPVAYHGLETREKASHVLRQGDIRFVFTSPLSSDAPAADFLAKHGDGVKDVAFRVE 80

                          90
                  ....*....|....*....
gi 1125492104  83 DISATFEELKRKGVRLISD 101
Cdd:cd08342    81 DADAAYERAVARGAKPVAE 99

C-terminal domain of 4-hydroxyphenylpyruvate dioxygenase (HppD) and hydroxymandelate synthase (HmaS); HppD and HmaS are non-heme iron-dependent dioxygenases, which modify a common substrate, 4-hydroxyphenylpyruvate (HPP), but yield different products. HPPD catalyzes the second reaction in tyrosine catabolism, the conversion of 4-hydroxyphenylpyruvate to homogentisate (2,5-dihydroxyphenylacetic acid, HG). HmaS converts HPP to 4-hydroxymandelate, a committed step in the formation of hydroxyphenylglycerine, a structural component of nonproteinogenic macrocyclic peptide antibiotics, such as vancomycin. If the emphasis is on catalytic chemistry, HPPD and HmaS are classified as members of a large family of alpha-keto acid dependent mononuclear non-heme iron oxygenases most of which require Fe(II), molecular oxygen, and an alpha-keto acid (typically alpha-ketoglutarate) to either oxygenate or oxidize a third substrate. Both enzymes are exceptions in that they require two, instead of three, substrates, do not use alpha-ketoglutarate, and incorporate both atoms of dioxygen into the aromatic product. Both HPPD and HmaS exhibit duplicate beta barrel topology in their N- and C-terminal domains which share sequence similarity, suggestive of a gene duplication. Each protein has only one catalytic site located in at the C-terminal domain. This HPPD_C_like domain represents the C-terminal domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1125492104   4 VDHLGIAVK--SIAQARRFYEQ-LGMKVM---DEEVVEHE----KLRAAMVPVGESRFELLEGT--SDDSVIAKFIAK-R 70
Cdd:cd07250     4 IDHVVGNVPdgEMDPAVEWYEKcLGFHRFwefDDEDIGTEysglRSIVLANPNETIKLPLNEPApgKRKSQIQEFLDYhG 83

                          90       100       110
                  ....*....|....*....|....*....|
gi 1125492104  71 GEGLHHVAVHVNDISATFEELKRKGVRLIS 100
Cdd:cd07250    84 GAGVQHIALNTDDIFATVRALRARGVEFLP 113

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 1125492104   3 KVDHLGIAVKSIAQARRFYEQLGMKVMDEEVVEHEKLRAAMVpvgeSRFelleGTSDDSVIAKfiaKRGEGLHHVAVHVN 82
Cdd:cd07256     3 RIDHFNQRVPDVDAGLRYYEDLGFRVSEYTEDDDGETWAAWM----HRK----GGVHDTALTN---GNGPRLHHVAFWVP 71

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1125492104  83 DISATFEELKRKGVRLISDEIKVGAGGH-------LYI 113
Cdd:cd07256    72 EPHNIIQTCDLMAAARYSDRIERGPGRHgvsnaffLYI 109

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 1125492104   9 IAVKSIAQARRFYEQLGMKvmdEEVVEHEKLRAAMVPVGESRFELLE-GTSDDSViakFIAKRGEGLHhVAVHVNDISAT 87
Cdd:cd07264     6 LYVDDFAASLRFYRDVLGL---PPRFLHEEGEYAEFDTGETKLALFSrKEMARSG---GPDRRGSAFE-LGFEVDDVEAT 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1125492104  88 FEELKRKGVRLISDEIKVGAGGHLYIFVHPsatGGVLLELCQ 129
Cdd:cd07264    79 VEELVERGAEFVREPANKPWGQTVAYVRDP---DGNLIEICE 117