Human glyoxalase domain-containing protein 5 and similar proteins; Uncharacterized subfamily of VOC family contains human glyoxalase domain-containing protein 5 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 515927853   2 IRRLDHIVLTVQHMEETIRFYTNVLGMKEETFGEGRKALRFGLQKINLHEAGHEFEPKAAHPKPGSADLCFITDLDIDSL 81
Cdd:cd07253    1 IKRLDHLVLTVKDIERTIDFYTKVLGMTVVTFKEGRKALRFGNQKINLHQKGKEFEPKASAPTPGSADLCFITETPIDEV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 515927853  82 LLHLRKQVVPIEEGPVRRSGALGPIESIYIRDPDMNLIEISRY 124
Cdd:cd07253   81 LEHLEACGVTIEEGPVKRTGALGPILSIYFRDPDGNLIELSNY 123

Human glyoxalase domain-containing protein 5 and similar proteins; Uncharacterized subfamily of VOC family contains human glyoxalase domain-containing protein 5 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 515927853   2 IRRLDHIVLTVQHMEETIRFYTNVLGMKEETFGEGRKALRFGLQKINLHEAGHEFEPKAAHPKPGSADLCFITDLDIDSL 81
Cdd:cd07253    1 IKRLDHLVLTVKDIERTIDFYTKVLGMTVVTFKEGRKALRFGNQKINLHQKGKEFEPKASAPTPGSADLCFITETPIDEV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 515927853  82 LLHLRKQVVPIEEGPVRRSGALGPIESIYIRDPDMNLIEISRY 124
Cdd:cd07253   81 LEHLEACGVTIEEGPVKRTGALGPILSIYFRDPDGNLIELSNY 123

Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 515927853    4 RLDHIVLTVQHMEETIRFYTNVLGMK--EETFGEGRKALRFGLQKIN--LHEAGHEFEPKAAHPKPGSADLCFITDL--D 77
Cdd:pfam00903   1 RIDHVALRVGDLEKSLDFYTDVLGFKlvEETDAGEEGGLRSAFFLAGgrVLELLLNETPPPAAAGFGGHHIAFIAFSvdD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 515927853   78 IDSLLLHLRKQVVPIEEGPVRRSGALGpieSIYIRDPDMNLIEI 121
Cdd:pfam00903  81 VDAAYDRLKAAGVEIVREPGRHGWGGR---YSYFRDPDGNLIEL 121

lactoylglutathione lyase; Lactoylglutathione lyase is also known as aldoketomutase and glyoxalase I. Glyoxylase I is a homodimer in many species. In some eukaryotes, including yeasts and plants, the orthologous protein carries a tandem duplication, is twice as long, and hits this model twice. [Central intermediary metabolism, Amino sugars, Energy metabolism, Other]

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 515927853    3 RRLDHIVLTVQHMEETIRFYTNVLGMK---EETFGEGRKALRF 42
Cdd:TIGR00068  16 RRLLHTMLRVGDLDKSLDFYTEVLGMKllrKRDFPEMKFSLAF 58

Human glyoxalase domain-containing protein 5 and similar proteins; Uncharacterized subfamily of VOC family contains human glyoxalase domain-containing protein 5 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 515927853   2 IRRLDHIVLTVQHMEETIRFYTNVLGMKEETFGEGRKALRFGLQKINLHEAGHEFEPKAAHPKPGSADLCFITDLDIDSL 81
Cdd:cd07253    1 IKRLDHLVLTVKDIERTIDFYTKVLGMTVVTFKEGRKALRFGNQKINLHQKGKEFEPKASAPTPGSADLCFITETPIDEV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 515927853  82 LLHLRKQVVPIEEGPVRRSGALGPIESIYIRDPDMNLIEISRY 124
Cdd:cd07253   81 LEHLEACGVTIEEGPVKRTGALGPILSIYFRDPDGNLIELSNY 123

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 515927853   2 IRRLDHIVLTVQHMEETIRFYTNVLGMKEETFGEGRKALRF--GLQKINLHEAGhefEPKAAHPKPGSADLCFITDL--D 77
Cdd:COG2514    1 ITRLGHVTLRVRDLERSAAFYTDVLGLEVVEREGGRVYLRAdgGEHLLVLEEAP---GAPPRPGAAGLDHVAFRVPSraD 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 515927853  78 IDSLLLHLRKQVVPIeEGPVRRSGAlgpiESIYIRDPDMNLIEISRYIEEADPS 131
Cdd:COG2514   78 LDAALARLAAAGVPV-EGAVDHGVG----ESLYFRDPDGNLIELYTDRPRFEHV 126

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 515927853   7 HIVLTVQHMEETIRFYTNVLGMKEETFGEGRKALRFGLQKiNLHEAGHEFEPKAAHPKPGSADLCFITDlDIDSLLLHLR 86
Cdd:cd06587    1 HVALRVPDLDASVAFYEEVLGFEVVSRNEGGGFAFLRLGP-GLRLALLEGPEPERPGGGGLFHLAFEVD-DVDEVDERLR 78

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 515927853  87 KQVVPIEEGPVRRSGALGpIESIYIRDPDMNLIEI 121
Cdd:cd06587   79 EAGAEGELVAPPVDDPWG-GRSFYFRDPDGNLIEF 112

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 515927853   1 MIRRLDHIVLTVQHMEETIRFYTNVLGMK-EETFGEGRKALRFGLQKinlhEAGHEFEPKAAHPKPGSADLCFITDlDID 79
Cdd:COG3324    1 MPGTIVWVELPVDDLERAKAFYEEVFGWTfEDDAGPGGDYAEFDTDG----GQVGGLMPGAEEPGGPGWLLYFAVD-DLD 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 515927853  80 SLLLHLRKQVVPIEEGPVRRSGAlGPIesIYIRDPDMNLIEI 121
Cdd:COG3324   76 AAVARVEAAGGTVLRPPTDIPPW-GRF--AVFRDPEGNRFGL 114

C-terminal domain of type I, class II extradiol dioxygenases, catalytic domain; This family contains the C-terminal, 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 515927853   6 DHIVLTVQHMEETIRFYTNVLGMK--EETFGEGRKALRFglQKINLHEAGHEFEPKAAhPKPGSADLCFITDlDIDSLLL 83
Cdd:cd08343    1 GHVVLCSPDVEASRDFYTDVLGFRvsDRIVDPGVDGGAF--LHCDRGTDHHTVALAGG-PHPGLHHVAFEVH-DLDDVGR 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 515927853  84 ---HLRKQVVPIEEGPVRRsgALGPIESIYIRDPDMNLIEISRYIEEADPS 131
Cdd:cd08343   77 ghdRLREKGYKIEWGPGRH--GLGSQVFDYWFDPSGNRVEYYTDGDLVDDD 125

N-terminal domain of human glyoxalase domain-containing protein 4 and similar proteins; Uncharacterized subfamily of the vicinal oxygen chelate (VOC) superfamily contains human glyoxalase domain-containing protein 4 and similar proteins. 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
                 ....*....|....*....|....*....|....*....|
gi 515927853   3 RRLDHIVLTVQHMEETIRFYTNVLGMK---EETFGEGRKA 39
Cdd:cd08358    1 RRALHFVFKVGDRNKTIKFYREILGMKvlrHEEFEEGCKA 40

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 515927853   9 VLTVQHMEETIRFYTNVLGMK------EETFgegrkaLRFGLQKINLH-EAGHEFEPKAahpkPGSAdlCFITDLDIDSL 81
Cdd:cd08349    3 ILPVRDIDKTLAFYVDVLGFEvdyerpPPGY------AILSRGGVELHlFEHPGLDPAG----SGVA--AYIRVEDIDAL 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 515927853  82 LLHLRKQVVPIEEGPvrrsgALGPIESI-------YIRDPDMNLI 119
Cdd:cd08349   71 HAELKAAGLPLFGIP-----RITPIEDKpwgmrefAVVDPDGNLL 110

metallothiol transferase FosB;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 515927853   1 MIRRLDHIVLTVQHMEETIRFYTNVLGmkEETFGEGRKALRFGLQK--INLHEAGH----EFEPKAAHpkpgsadLCF-I 73
Cdd:PRK04101   1 MLKGINHICFSVSNLEKSIEFYEKVLG--AKLLVKGRKTAYFDLNGlwIALNEEKDiprnEIHQSYTH-------IAFsI 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 515927853  74 TDLDIDSLLLHLRKQVVPIEEGpvrRSGALGPIESIYIRDPDMNLIE 120
Cdd:PRK04101  72 EEEDFDHWYQRLKENDVNILPG---RERDERDKKSIYFTDPDGHKFE 115

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

                         10        20        30
                 ....*....|....*....|....*....|..
gi 515927853   1 MIRRLDHIVLTVQ--HMEETIRFYTNVLGMKE 30
Cdd:COG3185  143 GLTRIDHIGIAVPrgDLDEWVLFYEDVLGFEE 174

lactoylglutathione lyase

                         10        20
                 ....*....|....*....|....*...
gi 515927853   2 IRRLDHIVLTVQHMEETIRFYTNVLGMK 29
Cdd:PLN02300  22 KRRMLHVVYRVGDLDRTIKFYTECLGMK 49

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 515927853   7 HIVLTVQHMEETIRFYTNVLGM---KEETFGEGR---------KALRFGLQKiNLHEAGHEFEPKAAHPKPGsadLCFIT 74
Cdd:cd07263    1 QVMLYVDDQDKALDFYVEKLGFevvEDVPMGGMRwvtvappgsPGTSLLLEP-KAHPAQMPQSPEAAGGTPG---ILLAT 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 515927853  75 DlDIDSLLLHLRKQVVPIEEGPVrrsgALGPIESIYIRDPDMNLIEI 121
Cdd:cd07263   77 D-DIDATYERLTAAGVTFVQEPT----QMGGGRVANFRDPDGNLFAL 118

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 515927853   5 LDHIVLTVQHMEETIRFYTNVLGMKEETFGEGRKA------LRFGLQKINLHEAGHEFEPKAA---HPKPGSADLCFITD 75
Cdd:cd07249    1 LDHIGIAVPDLDEALKFYEDVLGVKVSEPEELEEQgvrvafLELGNTQIELLEPLGEDSPIAKfldKKGGGLHHIAFEVD 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 515927853  76 lDIDSLLLHLRKQ-VVPIEEGPvrRSGALG 104
Cdd:cd07249   81 -DIDAAVEELKAQgVRLLSEGP--RIGAHG 107

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 515927853   8 IVLTVQHMEETIRFYTNVLGMKEE---TFGEGRKA---LRFGLQKINLHEAghefEPKAAHPKPGSADLCFITDlDIDSL 81
Cdd:COG2764    4 PYLVVDDAEEALEFYEDVFGFEVVfrmTDPDGKIMhaeLRIGGSVLMLSDA----PPDSPAAEGNGVSLSLYVD-DVDAL 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 515927853  82 LLHLRKQ----VVPIEE---GPvrRSGalgpiesiYIRDPDMNLIEIS 122
Cdd:COG2764   79 FARLVAAgatvVMPLQDtfwGD--RFG--------MVRDPFGVLWMIN 116

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 515927853   7 HIVLTVQHMEETIRFYTNVLGMKEEtfgEGRKALRFGLQKINLHEAGHEFEPKAAHPKPGSAD---LCF-ITDLDIDSLL 82
Cdd:cd08345    1 HITLIVRDLEKSTAFLQDIFGAREV---YSSGDKTFSLSKEKFFLLGGLWIALMEGESLQERSythIAFqIQSEDFDRYA 77

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 515927853  83 LHLRKQVVpiEEGPVRRSgALGPIESIYIRDPDMNLIE 120
Cdd:cd08345   78 ERLGALGV--EMRPPRPR-VEGEGRSIYFYDPDNHLFE 112

Glyoxalase I that uses Ni(++) as cofactor; This family includes Escherichia coil and other prokaryotic glyoxalase I that uses nickel 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
                 ....*....|....*....|...
gi 515927853   7 HIVLTVQHMEETIRFYTNVLGMK 29
Cdd:cd16358    3 HTMLRVGDLDRSIKFYTEVLGMK 25