vicinal oxygen chelate (VOC) family protein Bacillus subtilis YwkD and similar proteins; uncharacterized subfamily of vicinal oxygen chelate (VOC) family contains Bacillus subtilis YwkD 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 572994004   4 DAVHHIAIIGSDYDKTREFYVEKLGFEQVDEHIRPEKNDILFNVKKGNLILEIFIKPDAPMRPamPNPEHTGLRHLAFQV 83
Cdd:cd08352    1 KKIHHIAIICSDYEKSKDFYVDKLGFEIIREHYRPERNDIKLDLALGGYQLELFIKPDAPARP--SYPEALGLRHLAFKV 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 572994004  84 ADVEACLEEFDRLDIRHEVLRTDDFDGKKMAFFFDPDGLPLEIHE 128
Cdd:cd08352   79 EDVEATVAELKSLGIETEPIRVDDFTGKKFTFFFDPDGLPLELYE 123

vicinal oxygen chelate (VOC) family protein Bacillus subtilis YwkD and similar proteins; uncharacterized subfamily of vicinal oxygen chelate (VOC) family contains Bacillus subtilis YwkD 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 572994004   4 DAVHHIAIIGSDYDKTREFYVEKLGFEQVDEHIRPEKNDILFNVKKGNLILEIFIKPDAPMRPamPNPEHTGLRHLAFQV 83
Cdd:cd08352    1 KKIHHIAIICSDYEKSKDFYVDKLGFEIIREHYRPERNDIKLDLALGGYQLELFIKPDAPARP--SYPEALGLRHLAFKV 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 572994004  84 ADVEACLEEFDRLDIRHEVLRTDDFDGKKMAFFFDPDGLPLEIHE 128
Cdd:cd08352   79 EDVEATVAELKSLGIETEPIRVDDFTGKKFTFFFDPDGLPLELYE 123

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 572994004   6 VHHIAIIGSDYDKTREFYVEKLGFEQVDEHIRPEKNDILFNVKKGN-LILEIFIKPDAPmrpamPNPEHTGLRHLAFQVA 84
Cdd:COG0346    3 LHHVTLRVSDLEASLAFYTDVLGLELVKRTDFGDGGFGHAFLRLGDgTELELFEAPGAA-----PAPGGGGLHHLAFRVD 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 572994004  85 DVEACLEEFDRLDIRHEVLRTDDFDGKKMAFFFDPDGLPLEIHE 128
Cdd:COG0346   78 DLDAAYARLRAAGVEIEGEPRDRAYGYRSAYFRDPDGNLIELVE 121

vicinal oxygen chelate (VOC) family protein Bacillus subtilis YwkD and similar proteins; uncharacterized subfamily of vicinal oxygen chelate (VOC) family contains Bacillus subtilis YwkD 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 572994004   4 DAVHHIAIIGSDYDKTREFYVEKLGFEQVDEHIRPEKNDILFNVKKGNLILEIFIKPDAPMRPamPNPEHTGLRHLAFQV 83
Cdd:cd08352    1 KKIHHIAIICSDYEKSKDFYVDKLGFEIIREHYRPERNDIKLDLALGGYQLELFIKPDAPARP--SYPEALGLRHLAFKV 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 572994004  84 ADVEACLEEFDRLDIRHEVLRTDDFDGKKMAFFFDPDGLPLEIHE 128
Cdd:cd08352   79 EDVEATVAELKSLGIETEPIRVDDFTGKKFTFFFDPDGLPLELYE 123

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 572994004   6 VHHIAIIGSDYDKTREFYVEKLGFEQVDEHIRPEKNDILFNVKKGN-LILEIFIKPDAPmrpamPNPEHTGLRHLAFQVA 84
Cdd:COG0346    3 LHHVTLRVSDLEASLAFYTDVLGLELVKRTDFGDGGFGHAFLRLGDgTELELFEAPGAA-----PAPGGGGLHHLAFRVD 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 572994004  85 DVEACLEEFDRLDIRHEVLRTDDFDGKKMAFFFDPDGLPLEIHE 128
Cdd:COG0346   78 DLDAAYARLRAAGVEIEGEPRDRAYGYRSAYFRDPDGNLIELVE 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 572994004   8 HIAIIGSDYDKTREFYVEKLGFEQVDehiRPEKNDILFNVKKGNLILEIFIkpdapmRPAMPNPEHTGLRHLAFQVADVE 87
Cdd:cd06587    1 HVALRVPDLDASVAFYEEVLGFEVVS---RNEGGGFAFLRLGPGLRLALLE------GPEPERPGGGGLFHLAFEVDDVD 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 572994004  88 ACLEEFDRLDIRHEVL--RTDDFDGKKMAFFFDPDGLPLEI 126
Cdd:cd06587   72 EVDERLREAGAEGELVapPVDDPWGGRSFYFRDPDGNLIEF 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 572994004   5 AVHHIAIIGSDYDKTREFYVEKLGFEQV---------DEHIRPEKNDILFN---------VKKGNLI-LEIFIKPDAPMR 65
Cdd:cd16361    1 GVNHVGITVPDLDAAVEFYTDVLGAEVVyrstplaegDRGGGEMRAAGFVPgfarariamLRLGPGPgIELFEYKGPEQR 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 572994004  66 PAMPNPEHTGLRHLAFQVADVEACLEEFD------RLDIRhEVLRTDDFDGKKMAFFFDPDGLPLEI 126
Cdd:cd16361   81 APVPRNSDVGIFHFALQVDDVEAAAERLAaaggkvLMGPR-EIPDGGPGKGNRMVYLRDPWGTLIEL 146

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 572994004   5 AVHHIAIIGSDYDKTREFYVEKLGFEqVDEHIRPEKNDILFNVKKGnLILEIFIKPDAPMRPAMpnpehtglrHLAFQVA 84
Cdd:COG3324    4 TIVWVELPVDDLERAKAFYEEVFGWT-FEDDAGPGGDYAEFDTDGG-QVGGLMPGAEEPGGPGW---------LLYFAVD 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 572994004  85 DVEACLEEFDRLDIRHEVLRTDDFDGKKMAFFFDPDGLPLEIHE 128
Cdd:COG3324   73 DLDAAVARVEAAGGTVLRPPTDIPPWGRFAVFRDPEGNRFGLWQ 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 572994004   8 HIAIIGSDYDKTREFYVEKLGFEqvdehIRPEKNDILF-NVKKGNLILEIF-IKPDAPMRPAMPNPEHtglRHLAFQVAD 85
Cdd:cd07264    3 YIVLYVDDFAASLRFYRDVLGLP-----PRFLHEEGEYaEFDTGETKLALFsRKEMARSGGPDRRGSA---FELGFEVDD 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 572994004  86 VEACLEEFDRLDIRHEVLRTDDFDGKKMAFFFDPDGLPLEIHE 128
Cdd:cd07264   75 VEATVEELVERGAEFVREPANKPWGQTVAYVRDPDGNLIEICE 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 572994004  15 DYDKTREFYVEKLGFEQVDEHIRPEkNDILF-NVKKGNLILEIFikpDAPmrPAMPNPEHTGLrHLAFQVADVEAcleEF 93
Cdd:COG2764   10 DAEEALEFYEDVFGFEVVFRMTDPD-GKIMHaELRIGGSVLMLS---DAP--PDSPAAEGNGV-SLSLYVDDVDA---LF 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 572994004  94 DRL-----DIRHEVlrTDDFDGKKMAFFFDPDGLPLEIHE 128
Cdd:COG2764   80 ARLvaagaTVVMPL--QDTFWGDRFGMVRDPFGVLWMINT 117

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 572994004   6 VHHIAIIGSDYDKTREFYVEKLGFEQVDEHIRPEKNDILFNVKKGNLILEIF--IKPDAPMRPAMPNPeHTGLRHLAFQV 83
Cdd:cd07249    1 LDHIGIAVPDLDEALKFYEDVLGVKVSEPEELEEQGVRVAFLELGNTQIELLepLGEDSPIAKFLDKK-GGGLHHIAFEV 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 572994004  84 ADVEACLEEFDRLDIR--HEVLRtDDFDGKKMAFFFDPDG 121
Cdd:cd07249   80 DDIDAAVEELKAQGVRllSEGPR-IGAHGKRVAFLHPKDT 118

Glyoxalase I that uses Zn(++) as cofactor; This family includes eukaryotic glyoxalase I that prefers the divalent cation zinc 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        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 572994004  70 NPEHTGLRHLAFQVADVEACLEEFDRLDIRHeVLRTDDFDGKKMAFFFDPDGLPLEI 126
Cdd:cd07233   86 NSDPRGFGHIGIAVDDVYAACERFEELGVKF-KKKPDDGKMKGIAFIKDPDGYWIEI 141

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 572994004   8 HIAIIGSDYDKTREFYVEKLGFEQvdeHIRPEKNDILFNvkkGNLILEIFIKPDAPmrpamPNPEHTglrHLAFQVADve 87
Cdd:cd07244    4 HITLAVSDLERSLAFYVDLLGFKP---HVRWDKGAYLTA---GDLWLCLSLDPAAE-----PSPDYT---HIAFTVSE-- 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 572994004  88 aclEEFDRLDIRHEVLRTDDF-----DGKKMaFFFDPDGLPLEIH 127
Cdd:cd07244   68 ---EDFEELSERLRAAGVKIWqenssEGDSL-YFLDPDGHKLELH 108

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        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 572994004   8 HIAIIGSDYDKTREFYVEKLGFEQVDEhirpEKNDILF---NVKKGNLILEifikpdapmrpampNPEHTGLRHLAFQVA 84
Cdd:cd16360    1 YAELGVPDLEKALEFYTDVLGLQVAKR----DGNSVYLrgyEDEHHSLVLY--------------EAPEAGLKHFAFEVA 62

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 572994004  85 ---DVEACLEEFDRLDIRHEVLRTDDFDGKKMAF-FFDPDGLPLE 125
Cdd:cd16360   63 seeDLERAAASLTALGCDVTWGPDGEVPGGGKGFrFQDPSGHLLE 107

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 572994004   6 VHHIAIIGSDYDKTREFYVEKLGFEQVDEHIRPEKNDILFNVKKGNLILeIFIKPDAPMRPAMPNPEH--TGLRHLAFQV 83
Cdd:cd08342    1 FDHVEFYVGNAKQAASYYSTGLGFEPVAYHGLETREKASHVLRQGDIRF-VFTSPLSSDAPAADFLAKhgDGVKDVAFRV 79

                 ....*....
gi 572994004  84 ADVEACLEE 92
Cdd:cd08342   80 EDADAAYER 88

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 572994004   8 HIAIIGSDYDKTREFYVEKLGFEQV---DEHIRPEKNDILFNVkkGNLILEIFIKPDAPMRpampnpehtGLRHLAFQVA 84
Cdd:cd08345    1 HITLIVRDLEKSTAFLQDIFGAREVyssGDKTFSLSKEKFFLL--GGLWIALMEGESLQER---------SYTHIAFQIQ 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 572994004  85 DveaclEEFDRLDIRHEVL--------RTDDFDGKKMaFFFDPDGLPLEIH 127
Cdd:cd08345   70 S-----EDFDRYAERLGALgvemrpprPRVEGEGRSI-YFYDPDNHLFELH 114