fosfomycin resistance hydrolase FosXCC; FosXCC (FosX from Campylobacter coli) is rare, mobile antimicrobial resistance protein. Most members of the family are seen not only outside of the genus Campylobacter, but in Gram-positive species such as C. difficile.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A         4 GLSHITLIVKDLNKTTAFLQNIFNAEEIYSSGDKTFSLSKEKFFLIAGLWICIMEGDSLqERTYNHIAFQIQSEEVDEYT 83
Cdd:NF041542   2 GISHITFIVKDLDKATKFFKEIFEAKEIYSSEDKTFSISKEKFFLINDLWIAVMEGEKI-EKSYNHIAFKIDESDYEMYL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
2P7O_A        84 ERIKALGVEMKPERPRVQGEGRSIYFYDFDNHLFELHAGTLEERLKRYHE 133
Cdd:NF041542  81 KRIENLGLEIKSGRKRVIGEGNSIYFYDYDNHLFELHTGTLETRLLRYQK 130

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        4 GLSHITLIVKDLNKTTAFLQNIFNAEEI--YSSGDKTFSLskekFFLIAG--LWICIMEGDSLQERT----YNHIAFQIq 75
Cdd:COG0346   2 GLHHVTLRVSDLEASLAFYTDVLGLELVkrTDFGDGGFGH----AFLRLGdgTELELFEAPGAAPAPggggLHHLAFRV- 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
2P7O_A       76 sEEVDEYTERIKALGVEMKPErPRVQGEG-RSIYFYDFDNHLFELH 120
Cdd:COG0346  77 -DDLDAAYARLRAAGVEIEGE-PRDRAYGyRSAYFRDPDGNLIELV 120

Fosfomycin resistant protein; This family contains three types of fosfomycin resistant protein. Fosfomycin inhibits the enzyme UDP-N-acetylglucosamine-3-enolpyruvyltransferase (MurA), which catalyzes the first committed step in bacterial cell wall biosynthesis. The three types of fosfomycin resistance proteins, employ different mechanisms to render fosfomycin [(1R,2S)-epoxypropylphosphonic acid] inactive. FosB catalyzes the addition of L-cysteine to the epoxide ring of fosfomycin. FosX catalyzes the addition of a water molecule to the C1 position of the antibiotic with inversion of configuration at C1. FosA catalyzes the addition of glutathione to the antibiotic fosfomycin, making it inactive. Catalytic activities of both FosX and FosA are Mn(II)-dependent, but FosB is activated by Mg(II). Fosfomycin resistant proteins are evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        7 HITLIVKDLNKTTAFLQNIFNAEEIYSSGDKTFSLSKEKFFLIAGLWICIMEGDSLQERTYNHIAFQIQSEEVDEYTERI 86
Cdd:cd08345   1 HITLIVRDLEKSTAFLQDIFGAREVYSSGDKTFSLSKEKFFLLGGLWIALMEGESLQERSYTHIAFQIQSEDFDRYAERL 80

                        90       100       110
                ....*....|....*....|....*....|....*...
2P7O_A       87 KALGVEMKPERPRVQGEGRSIYFYDFDNHLFELHAGTL 124
Cdd:cd08345  81 GALGVEMRPPRPRVEGEGRSIYFYDPDNHLFELHTGTL 118

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        5 LSHITLIVKDLNKTTAFLQNIFNAEeIYSSGDKTfslskeKFFLIAGLWICIMEGDSLQER----TYNHIAFQIQSEEVD 80
Cdd:cd08363   1 INHITFSVSNLNKSIAFYKDVLDAK-LLVLGEKT------AYFDLNGLWLALNVQEDIPRNeishSYTHIAFSIDEEDLD 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
2P7O_A       81 EYTERIKALGVEMKPERPRVQGEGRSIYFYDFDNHLFELHAGTLEERLKRYHE 133
Cdd:cd08363  74 AFKERLKDNGVNILEGRKRDILEGQSIYFTDPDGHLFELHTGTLEDRLEYYKE 126

fosfomycin resistant protein subfamily FosA; This subfamily family contains FosA, a fosfomycin resistant protein. FosA is a Mn(II) and K(+)-dependent glutathione transferase. Fosfomycin inhibits the enzyme UDP-N-acetylglucosamine-3-enolpyruvyltransferase (MurA), which catalyzes the first committed step in bacterial cell wall biosynthesis. FosA, catalyzes the addition of glutathione to the antibiotic fosfomycin, (1R,2S)-epoxypropylphosphonic acid, making it inactive. FosA is a Mn(II) dependent enzyme. It is evolutionarily related to glyoxalase I and type I extradiol dioxygenases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        4 GLSHITLIVKDLNKTTAFLQNI--FNAEEIYSSGdktfslskeKFFLIAGLWICI-MEGDSLQERTYNHIAFQIQSEEVD 80
Cdd:cd07244   1 GINHITLAVSDLERSLAFYVDLlgFKPHVRWDKG---------AYLTAGDLWLCLsLDPAAEPSPDYTHIAFTVSEEDFE 71

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
2P7O_A       81 EYTERIKALGVEMKPERprvQGEGRSIYFYDFDNHLFELHAGTLEERLKRYHE 133
Cdd:cd07244  72 ELSERLRAAGVKIWQEN---SSEGDSLYFLDPDGHKLELHVGSLESRLASLRE 121

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        7 HITLIVKDLNKTTAFLQNIFNAEEIYSSGDKTFSLskekFFLIAGLWICIMEGDSLQERT---YNHIAFQIQSEEVDEYT 83
Cdd:cd06587   1 HVALRVPDLDASVAFYEEVLGFEVVSRNEGGGFAF----LRLGPGLRLALLEGPEPERPGgggLFHLAFEVDDVDEVDER 76

                        90       100       110
                ....*....|....*....|....*....|....*.
2P7O_A       84 ERIKALGVEMKPERPRVQGEGRSIYFYDFDNHLFEL 119
Cdd:cd06587  77 LREAGAEGELVAPPVDDPWGGRSFYFRDPDGNLIEF 112

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A          4 GLSHITLIVKDLNKTTAFLQNIFNAEEIYSSGDKTFSLSKEKFFLIAGLWICIM----EGDSLQERTYNHIAFQ-IQSEE 78
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKLVEETDAGEEGGLRSAFFLAGGRVLELLlnetPPPAAAGFGGHHIAFIaFSVDD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
2P7O_A         79 VDEYTERIKALGVEMKPERPRVQGEGRSIYFYDFDNHLFEL 119
Cdd:pfam00903  81 VDAAYDRLKAAGVEIVREPGRHGWGGRYSYFRDPDGNLIEL 121

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        1 MISGLSHITLIVKDLNKTTAFLQNIFNAE-EIYSSGDKTFSLskekFFLIAGLWICIMEGDSLQERTYNHIAFQiqSEEV 79
Cdd:COG3324   1 MPGTIVWVELPVDDLERAKAFYEEVFGWTfEDDAGPGGDYAE----FDTDGGQVGGLMPGAEEPGGPGWLLYFA--VDDL 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
2P7O_A       80 DEYTERIKALGVEMKPERPRVQGEGRSIYFYDFDNHLFELH 120
Cdd:COG3324  75 DAAVARVEAAGGTVLRPPTDIPPWGRFAVFRDPEGNRFGLW 115

vicinal oxygen chelate (VOC) family protein similar to Bacillus subtilis YyaH; 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        5 LSHITLIVKDLNKTTAFLQNIFNAE--EIYSSGDKTFslskEKFFLI--AGLWICIMEGDSLQ------ERT-YNHIAFQ 73
Cdd:cd07241   2 IEHVALWTNDLERMKDFYVKYFGAEsnDIYHNKKKGF----RSYFLTfdSGARLELMSRPDVTdpdkevERTgLAHIAFS 77

                        90       100       110
                ....*....|....*....|....*....|..
2P7O_A       74 IQS-EEVDEYTERIKALGVEMKPErPRVQGEG 104
Cdd:cd07241  78 VGSkEAVDELTERLRADGYAVVGG-PRTTGDG 108

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        8 ITLIVKDLNKTTAFlqnifnaeeiYSSGDKTFSLSKEK---FFLIAGLWICIMEGDSLQE------RTYNH----IAFQI 74
Cdd:cd07251   2 ITLGVRDLERSARF----------YEALGWKPNLDPNDgvvFFQLGGTVLALYPRDALAEdagvsvTGAGFsgvtLAHNV 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
2P7O_A       75 QS-EEVDEYTERIKALGVEMKPERPRVQGEGRSIYFYDFDNHLFEL 119
Cdd:cd07251  72 RSrEEVDQLLAKAVAAGGKILKPPQEVFWGGYSGYFADPDGHIWEV 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        7 HITLIVKDLNKTTAFLQNIFNAEEIYSSGDktfsLSKekfFLIA--GLWICIMEGDSLQERTYNHIAFQIQS-EEVDEYT 83
Cdd:cd07254   4 HLSLNVTDLERSIRFYSDLFGAEPAKRKAD----YAK---FMLEdpPLNLALLVNDRKEPYGLNHLGIQVDSkEEVAALK 76

                        90
                ....*....|....
2P7O_A       84 ERIKALGVEMKPER 97
Cdd:cd07254  77 ARAEAAGLPVRKEP 90

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2P7O_A        5 LSHITLIVKDLNKTTAFLQNIFNAEEIYSSGDKTFSLskekfFLIAGLWICI-----MEGDSLQERTYNHIAFQIQSEEV 79
Cdd:cd07264   1 IAYIVLYVDDFAASLRFYRDVLGLPPRFLHEEGEYAE-----FDTGETKLALfsrkeMARSGGPDRRGSAFELGFEVDDV 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
2P7O_A       80 DEYTERIKALGVEMKPERPRVQGEGRSIYFYDFDNHLFELH 120
Cdd:cd07264  76 EATVEELVERGAEFVREPANKPWGQTVAYVRDPDGNLIEIC 116