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 1464571673  14 HSGMVAKDLDETIAFYTEKLGFEVagIFHNGENRCAFLRYG-HLTIETWEG-EPAPMTAGAINHWAFDTPDIEAAFENAK 91
Cdd:cd06587     1 HVALRVPDLDASVAFYEEVLGFEV--VSRNEGGGFAFLRLGpGLRLALLEGpEPERPGGGGLFHLAFEVDDVDEVDERLR 78

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1464571673  92 ELGLKFKDTEIQHIDSFwehGIRFFNVYGPNGETIEF 128
Cdd:cd06587    79 EAGAEGELVAPPVDDPW---GGRSFYFRDPDGNLIEF 112

VOC family protein;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1464571673  13 QHSGMVAKDLDETIAFYTEKLGFEVAGIFHNGEN---RCAFLRYGHLTIETWE-----GEPAPMTAGAINHWAFDTPDIE 84
Cdd:PRK11478    8 HHIAIIATDYAVSKAFYCDILGFTLQSEVYREARdswKGDLALNGQYVIELFSfpfppERPSRPEACGLRHLAFSVDDID 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1464571673  85 AAFENAKELGLKfkdTEIQHIDSFWEHGIRFFNvyGPNGETIEFCQ 130
Cdd:PRK11478   88 AAVAHLESHNVK---CEAIRVDPYTQKRFTFFN--DPDGLPLELYE 128

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 1464571673  14 HSGMVAKDLDETIAFYTEKLGFEVagIFHNGENRCAFLRYG-HLTIETWEG-EPAPMTAGAINHWAFDTPDIEAAFENAK 91
Cdd:cd06587     1 HVALRVPDLDASVAFYEEVLGFEV--VSRNEGGGFAFLRLGpGLRLALLEGpEPERPGGGGLFHLAFEVDDVDEVDERLR 78

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1464571673  92 ELGLKFKDTEIQHIDSFwehGIRFFNVYGPNGETIEF 128
Cdd:cd06587    79 EAGAEGELVAPPVDDPW---GGRSFYFRDPDGNLIEF 112

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 1464571673  13 QHSGMVAKDLDETIAFYTEKLGFEVAGIFHNGEN--RCAFLRYGHLTIETWE--GEPAPMTA------GAINHWAFDTPD 82
Cdd:cd07249     2 DHIGIAVPDLDEALKFYEDVLGVKVSEPEELEEQgvRVAFLELGNTQIELLEplGEDSPIAKfldkkgGGLHHIAFEVDD 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1464571673  83 IEAAFENAKELGLKFKDTEIQHIDSfwEHGIRFFNVYGPNGETIEFCQ 130
Cdd:cd07249    82 IDAAVEELKAQGVRLLSEGPRIGAH--GKRVAFLHPKDTGGVLIELVE 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1464571673  18 VAKDLDETIAFYTEKLGFEVAGIFHNGENRCAF--LRYGHLTI---ETWEGEPAPMTAGAINHwaFDTPDIEAAFENAKE 92
Cdd:COG2764     7 VVDDAEEALEFYEDVFGFEVVFRMTDPDGKIMHaeLRIGGSVLmlsDAPPDSPAAEGNGVSLS--LYVDDVDALFARLVA 84

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1464571673  93 LGLKFkDTEIQhiDSFWehGIRFFNVYGPNGETIEFCQ 130
Cdd:COG2764    85 AGATV-VMPLQ--DTFW--GDRFGMVRDPFGVLWMINT 117

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1464571673  10 TDFQHSGMVAKDLDETIAFYTEKLGFEVAGifhnGENRCAFLR----YGHLTIETWEGEPAPMTAGAINHWAFDTP---D 82
Cdd:COG2514     2 TRLGHVTLRVRDLERSAAFYTDVLGLEVVE----REGGRVYLRadggEHLLVLEEAPGAPPRPGAAGLDHVAFRVPsraD 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1464571673  83 IEAAFENAKELGLKFKDTEiqhidsfwEHGI-RFFNVYGPNGETIEF 128
Cdd:COG2514    78 LDAALARLAAAGVPVEGAV--------DHGVgESLYFRDPDGNLIEL 116

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 1464571673  20 KDLDETIAFYTEKLGFEVAGIFHNGE------NRCAFLRYGHLTIETWEGEPAPMTAGAInhwAFDTPDIEAAFENAKEL 93
Cdd:cd07264     9 DDFAASLRFYRDVLGLPPRFLHEEGEyaefdtGETKLALFSRKEMARSGGPDRRGSAFEL---GFEVDDVEATVEELVER 85

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1464571673  94 GLKFKdteIQHIDSfwEHGIRFFNVYGPNGETIEFCQ 130
Cdd:cd07264    86 GAEFV---REPANK--PWGQTVAYVRDPDGNLIEICE 117

Bleomycin binding protein (BLMA) and similar proteins; BLMA also called Bleomycin resistance protein, confers Bm resistance by directly binding to Bm. Bm is a glycopeptide antibiotic produced naturally by actinomycetes. It is a potent anti-cancer drug, which acts as a strong DNA-cutting agent, thereby causing cell death. BLMA is produced by actinomycetes to protect themselves against their own lethal compound. BLMA has two identically-folded subdomains, with the same alpha/beta fold; these two halves have no sequence similarity. BLMAs are dimers and each dimer binds to two Bm molecules at the Bm-binding pockets formed at the dimer interface; two Bm molecules are bound per dimer. BLMA belongs to a conserved domain superfamily that is found in a variety of structurally related metalloproteins, including the bleomycin resistance protein, glyoxalase I, and type I ring-cleaving dioxygenases. As for the larger superfamily, this family contains members with or without domain swapping.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1464571673  21 DLDETIAFYTEKLGFEVAgiFHNGENRCAFLRYGHLTIETWEGEPAPMTAGAINHWaFDTPDIEAAFENAKELGLKFKDT 100
Cdd:cd08349     8 DIDKTLAFYVDVLGFEVD--YERPPPGYAILSRGGVELHLFEHPGLDPAGSGVAAY-IRVEDIDALHAELKAAGLPLFGI 84

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1464571673 101 EIQH--IDSFWehGIRFFNVYGPNGETIEFCQ 130
Cdd:cd08349    85 PRITpiEDKPW--GMREFAVVDPDGNLLRFGQ 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 1464571673  21 DLDETIAFYTEKLGFEVAGIFHNGENR-----------CAFLRY--GHLTIETWEGEPAPMTAGAInhwaFDTPDIEAAF 87
Cdd:cd07263     8 DQDKALDFYVEKLGFEVVEDVPMGGMRwvtvappgspgTSLLLEpkAHPAQMPQSPEAAGGTPGIL----LATDDIDATY 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1464571673  88 ENAKELGLKFkDTEIQHIDsfwehGIRFFNVYGPNGETIEFCQ 130
Cdd:cd07263    84 ERLTAAGVTF-VQEPTQMG-----GGRVANFRDPDGNLFALME 120

VOC family protein;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1464571673  13 QHSGMVAKDLDETIAFYTEKLGFEVAGIFHNGEN---RCAFLRYGHLTIETWE-----GEPAPMTAGAINHWAFDTPDIE 84
Cdd:PRK11478    8 HHIAIIATDYAVSKAFYCDILGFTLQSEVYREARdswKGDLALNGQYVIELFSfpfppERPSRPEACGLRHLAFSVDDID 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1464571673  85 AAFENAKELGLKfkdTEIQHIDSFWEHGIRFFNvyGPNGETIEFCQ 130
Cdd:PRK11478   88 AAVAHLESHNVK---CEAIRVDPYTQKRFTFFN--DPDGLPLELYE 128

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1464571673  19 AKDLDETIAFYTEKLGFEVAgIFHNGENRCAFLRYGHLTIetweG---EPAPMTAGAINHWA--FDTPDIEAAFENAKEL 93
Cdd:cd07247     8 TTDLERAKAFYGAVFGWTFE-DEGDGGGDYALFTAGGGAV----GglmRAPEEVAGAPPGWLiyFAVDDLDAALARVEAA 82

                  .
gi 1464571673  94 G 94
Cdd:cd07247    83 G 83