Bradyrhizobium japonicum BLR2406 and related proteins, cupin domain; This family includes bacterial and fungal proteins homologous to BLR2406, a Bradyrhizobium japonicum protein of unknown function with a cupin beta barrel domain. Proteins in this subfamily appear to align closest to RmlC carbohydrate epimerase which is involved in dTDP-L-rhamnose production, and belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488811425  25 VSAQSVGSQGICMHLLTIPPGGRARAHKHASHETAIYVLEGETVMFWGERLEHRMEVGAGELLYIPADMPHLPMNLS-DR 103
Cdd:cd02210    1 ISAETVGAKGLWMGVVTIPPGARTGAHHHGEHETAIYVLSGRAETRYGDRLEHRAEAGPGDFIYIPPGVPHQEVNLSdDE 80

                         90
                 ....*....|....*..
gi 488811425 104 PAVAVISRTDPNEQESV 120
Cdd:cd02210   81 PAVAVVARSDPEEQEVV 97

Cupin; This family represents the conserved barrel domain of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel). This family contains 11S and 7S plant seed storage proteins, and germins. Plant seed storage proteins provide the major nitrogen source for the developing plant.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488811425    33 QGICMHLLTIPPGGRARAHKH-ASHEtAIYVLEGE-TVMFWGERLEHRM--EVGAGELLYIPADMPHLPMNLSDRPAVAV 108
Cdd:smart00835  28 LGISAARVNLEPGGMLPPHYHpRATE-LLYVVRGEgRVGVVDPNGNKVYdaRLREGDVFVVPQGHPHFQVNSGDENLEFV 106

                           90
                   ....*....|
gi 488811425   109 ISRT-DPNEQ 117
Cdd:smart00835 107 AFNTnDPNRR 116

Bradyrhizobium japonicum BLR2406 and related proteins, cupin domain; This family includes bacterial and fungal proteins homologous to BLR2406, a Bradyrhizobium japonicum protein of unknown function with a cupin beta barrel domain. Proteins in this subfamily appear to align closest to RmlC carbohydrate epimerase which is involved in dTDP-L-rhamnose production, and belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488811425  25 VSAQSVGSQGICMHLLTIPPGGRARAHKHASHETAIYVLEGETVMFWGERLEHRMEVGAGELLYIPADMPHLPMNLS-DR 103
Cdd:cd02210    1 ISAETVGAKGLWMGVVTIPPGARTGAHHHGEHETAIYVLSGRAETRYGDRLEHRAEAGPGDFIYIPPGVPHQEVNLSdDE 80

                         90
                 ....*....|....*..
gi 488811425 104 PAVAVISRTDPNEQESV 120
Cdd:cd02210   81 PAVAVVARSDPEEQEVV 97

Cupin domain; This family represents the conserved barrel domain of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 488811425   38 HLLTIPPGGRARAHKHASHETAIYVLEGEtVMFWGErlEHRMEVGAGELLYIPADMPHLPMNLSDRPAVAV 108
Cdd:pfam07883   1 GLVTLPPGESSPPHRHPGEDEFFYVLEGE-GELTVD--GEEVVLKAGDSVYFPAGVPHRFRNTGDEPARLL 68

Mannose-6-phosphate isomerase, cupin superfamily [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 488811425  31 GSQGICMHLLTIPPGGRARAHKHASHETAIYVLEGETVMFWGERlehRMEVGAGELLYIPADMPHLPMNLSDRPAV 106
Cdd:COG0662   23 GGERLSVKRITVPPGAELSLHVHPHRDEFFYVLEGTGEVTIGDE---EVELKAGDSVYIPAGVPHRLRNPGDEPLE 95

Thermotoga maritima TM1459 and related proteins, cupin domain; This family includes bacterial and archaeal proteins homologous to Thermotoga maritima TM1459, a manganese-containing cupin that has been shown to cleave C=C bonds in the presence of alkylperoxide as oxidant in vitro. Its biological function is still unknown. This family also includes Halorhodospira halophila Hhal_0468. Structures of these proteins show a cupin fold with a conserved "jelly roll-like" beta-barrel fold that form a homodimer.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 488811425  31 GSQGICMHLLTIPPGGRARAHKHAsHETAIYVLEGETVMFWGERlEHrmEVGAGELLYIPADMPH 95
Cdd:cd02222   13 GAPNFAMRYFEIEPGGHTPLHTHP-WEHEVYVLRGKGVVVIGGE-EY--PVKPGDVVYIPPNEPH 73

XRE (Xenobiotic Response Element) family transcriptional regulators, C-terminal cupin domain; This family contains transcriptional regulators containing an N-terminal XRE (Xenobiotic Response Element) family helix-turn-helix (HTH) DNA-binding domain and a C-terminal cupin domain. Included in this family is Escherichia coli transcription factor SutR (YdcN) that plays a regulatory role in sulfur utilization; it regulates a set of genes involved in the generation of sulfate and its reduction, the synthesis of cysteine, the synthesis of enzymes containing Fe-S as cofactors, and the modification of tRNA with use of sulfur-containing substrates. This family belongs to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 488811425  37 MHLLTIPPGG-RARAHKHASHEtAIYVLEGETVMFWGERlehRMEVGAGELLYIPADMPHLPMNLSDRPAVAV 108
Cdd:cd02209   18 PFLVTLPPGGsGGEPYSHEGEE-FGYVLEGELELTVGGE---TYVLEAGDSIYFDSDVPHRYRNPGDEPARVL 86

Oxalate decarboxylase (OxDC), cupin domain; Oxalate decarboxylase (OxDC; EC 4.1.1.2) is a manganese-dependent bicupin that catalyzes the conversion of oxalate to formate and carbon dioxide, utilizing dioxygen as a cofactor. It is evolutionarily related to oxalate oxidase (OxOx or germin; EC 1.2.3.4) which, in contrast, converts oxalate and dioxygen to carbon dioxide and hydrogen peroxide. OxDC is classified as a bicupin because it contains two cupin folds and both domains are included in this alignment. Each OxDC cupin domain contains one manganese binding site, with four manganese binding residues (three histidines and one glutamate) conserved as well as a number of hydrophobic residues. Members of this family belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488811425  32 SQGICMHLLTIPPGGRARAHKHASHETAIYVLEGE---TVMFWGERLEhRMEVGAGELLYIPADMPHLPMNLSDRPAVAV 108
Cdd:cd02240   24 SKDLSSALVRVAPGAMRELHWHPNTAEWQYVISGSarvTVFDEDGRFE-TFNLGAGDVGYVPSGSGHHIENIGDEDAEFL 102

                 ....*.
gi 488811425 109 ISRTDP 114
Cdd:cd02240  103 LIFDDG 108

Cupin; This family represents the conserved barrel domain of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel). This family contains 11S and 7S plant seed storage proteins, and germins. Plant seed storage proteins provide the major nitrogen source for the developing plant.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488811425   34 GICMHLLTIPPGGRARAHKHASHETAIYVLEGE-TVMF----WGERLEHRmEVGAGELLYIPADMPHLPMNLSDRPAVAV 108
Cdd:pfam00190  32 GISAARVDLAPGGMNPPHWHPNATEILYVLQGRgRVGFvvpgNGNRVFHK-VLREGDVFVVPQGLPHFQYNIGDEPAVAF 110

                          90
                  ....*....|...
gi 488811425  109 IS-RTDPNEQESV 120
Cdd:pfam00190 111 VAfDTNNPGNQSI 123

Oxalate decarboxylase/archaeal phosphoglucose isomerase, cupin superfamily [Carbohydrate transport and metabolism]; Oxalate decarboxylase/archaeal phosphoglucose isomerase, cupin superfamily is part of the Pathway/BioSystem: Glycolysis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488811425  37 MHL----LTIPPGGRARAHKHASHETAIYVLEGE---TVMFWGERLEHrMEVGAGELLYIPADMPHLPMNLSDRPAVAVI 109
Cdd:COG2140    1 MTLagglTVLEPGGVREEHWHPNAAEWYYVLSGEarmTVQDPPGRART-VDVGPGDVVYVPPGYGHYIINTGDEPLVFLA 79

                         90
                 ....*....|....*
gi 488811425 110 SRTDPNEQESVTLLP 124
Cdd:COG2140   80 VFDDDAGSDYGTISL 94

Bacillus subtilis bacilysin and related proteins, cupin domain; Bacilysin (BacB, also known as AerE in Microcystis aeruginosa) is a non-ribosomally synthesized dipeptide antibiotic that is produced and excreted by certain strains of Bacillus subtilis. It is an oxidase that catalyzes the synthesis of 2-oxo-3-(4-oxocyclohexa-2,5-dienyl)propanoic acid, a precursor to L-anticapsin. Each bacilysin monomer has two tandem cupin domains. It is active against a wide range of bacteria and some fungi. The antimicrobial activity of bacilysin is antagonized by glucosamine and N-acetyl glucosamine, indicating that bacilysin interferes with glucosamine synthesis, and thus, with the synthesis of microbial cell walls. AerE is thought to be involved in the formation of the 2-carboxy-6-hydroxyoctahydroindole (Choi) moiety found on all aeruginosin tetrapeptides, based on gene knock-out experiments. It is encoded by the aerE gene of the aerABCDEF aeruginosin biosynthesis gene cluster in Microcystis aeruginosa.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488811425  22 NEGVSAQSVGSQGICMHLLTIPPGGRARAHKHASHETAIyVLEGETVMFWGERlEHRMEVgAGELLYIPADMPHLPMNLS 101
Cdd:cd06975    6 ETGVELQFFVGSWTEIMLSYIPPGAKMPLHQHREEQIGM-ILNGELEMTVGGE-EQELEP-LGDVYYAPPNVPHGAVNPS 82

                 ....*..
gi 488811425 102 DRPAVAV 108
Cdd:cd06975   83 DETAVLL 89

Bradyrhizobium diazoefficiens BLL4011 and related proteins, cupin domain; This family includes bacterial and fungal proteins homologous to BLL4011, a Bradyrhizobium diazoefficiens protein of unknown function. Proteins in this family belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 488811425  42 IPPGGRARAHKHASHETAiYVLEGETVMFWGERLEHRmeVGAGELLYIPADMPHLPMNLSDRPAVAVI 109
Cdd:cd02235   26 IPPGAVAGRHTHPGEESG-YVLEGSLELEVDGQPPVT--LKAGDSFFIPAGTVHNAKNVGSGPAKLLA 90

Bacillus subtilis bacilysin and related proteins, C-terminal cupin domain; This model represents the C-terminal domain of bacilysin (BacB, also known as AerE in Microcystis aeruginosa), a non-ribosomally synthesized dipeptide antibiotic that is produced and excreted by certain strains of Bacillus subtilis. Bacilysin is an oxidase that catalyzes the synthesis of 2-oxo-3-(4-oxocyclohexa-2,5-dienyl)propanoic acid, a precursor to L-anticapsin. Each bacilysin monomer has two tandem cupin domains. It is active against a wide range of bacteria and some fungi. The antimicrobial activity of bacilysin is antagonized by glucosamine and N-acetyl glucosamine, indicating that bacilysin interferes with glucosamine synthesis, and thus, with the synthesis of microbial cell walls. AerE is thought to be involved in the formation of the 2-carboxy-6-hydroxyoctahydroindole (Choi) moiety found on all aeruginosin tetrapeptides, based on gene knock-out experiments. It is encoded by the aerE gene of the aerABCDEF aeruginosin biosynthesis gene cluster in Microcystis aeruginosa. Proteins in this family belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 488811425  39 LLTIPPGGRARAHKHASHETAIyVLEGETVMFWGErlEHRmEVGAGELLYIPADMPHLPMNLSDRPA 105
Cdd:cd10547   23 ISQIPPGGKMPLHQHRGEQIGI-ILNGKYDMTVGG--EEQ-ELGYGKIYYAPPNVSHSGYNDSDETA 85

Streptomyces resistomycificus RemF cyclase and related proteins, cupin domain; RemF cyclase is a manganese-containing polyketide cyclase present in bacteria that is involved in the biosynthesis of resistomycin, the aromatic pentacyclic metabolite in Streptomyces resistomycificus. Structure of this enzyme shows a cupin fold with a conserved "jelly roll-like" beta-barrel fold that forms a homodimer. It contains an unusual octahedral zinc-binding site in a large hydrophobic pocket that may represent the active site. The zinc ion, coordinated to four histidine side chains and two water molecules, could act as a Lewis acid in the aldol condensation reaction catalyzed by RemF, reminiscent of class II aldolases.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 488811425  37 MHLLTIPPGGRARA-HKHASHETAIYVLEGE-TVMFWGERlehrMEVGAGELLYIPADMPHLPMNLSDRPA 105
Cdd:cd06979   19 LFEFEVSPNAGMPPpHYHEDWEETIYGLEGSvTLTLPGKT----VEVGPGDSIFIPRGEVHGFVNRSGGPT 85

quercetinase, N- and C-terminal cupin domains; This family contains quercetinase (also known as quercetin 2,3-dioxygenase, 2,3QD, QDO and YxaG; EC 1.13.11.24), a mononuclear copper-dependent dioxygenase that catalyzes the cleavage of the flavonol quercetin (5,7,3',4'-tetrahydroxyflavonol) heterocyclic ring to produce 2-protocatechuoyl-phloroglucinol carboxylic acid and carbon monoxide. Bacillus subtilis quercetin 2,3-dioxygenase (QDO) is a homodimer that shows oxygenase activity with several divalent metals such as Mn2+, Co2+, Fe2+, and Cu2+, although the preferred one appears to be Mn2+. The dioxygen binds to the metal ion of the Cu-QDO-quercetin complex, yielding a Cu2+-superoxo quercetin radical intermediate, which then forms a Cu2+-alkylperoxo complex which then evolves into endoperoxide intermediate that decomposes to the product. Quercetinase is a bicupin with two tandem cupin beta-barrel domains, both of which are included in this alignment model. The pirins, which also belong to the cupin domain family, have been shown to catalyze a reaction involving quercetin and may have a function similar to that of quercetinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488811425  15 GRQGFTYNegVSAQSVGSQgICMHLLTIPPGGRARAHKHASHETAIYVLEGEtVMFWGERlEHRMeVGAGELLYIPADMP 94
Cdd:cd02215   15 GGQLFTVL--ATGESTGGA-FTLVTTEGPKGDAIPPHYHKRHHETFYVLEGR-LQLWLDG-ESRL-LTPGDFASVPPGTI 88

                 .
gi 488811425  95 H 95
Cdd:cd02215   89 H 89

Helicobacter pylori HP0902 and related proteins, cupin domain; This family includes prokaryotic and archaeal proteins homologous to HP0902, a functionally uncharacterized protein from Helicobacter pylori and Spy1581, a protein of unknown function from Streptococcus pyogenes. These proteins demonstrate all-beta cupin folds that cannot bind metal ions due to the absence of a metal-binding histidine that is conserved in many metallo-cupins. HP0902 is able to bind bacterial endotoxin lipopolysaccharides (LPS) through its surface-exposed loops, where metal-binding sites are usually found in other metallo-cupins, and thus may have a putative role in H. pylori pathogenicity.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 488811425  51 HKhASHETAIYVLEGETVMFWGERlEHRMEvgAGELLYIPADMPH 95
Cdd:cd02230   27 HT-APGDATVQVLEGEAEFTIGGE-TVTLK--AGELIVMPANVPH 67

Ureidoglycine aminohydrolase [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 488811425  36 CMHLLTIPPGGRARAHKHASH-ETAIYVLEGE-TVMFWGErlEHRMEvgAGELLYIPADMPHLPMNLSDRPA 105
Cdd:COG3257   60 SQYIVEVAPGGGSDRPEPDPGaETFLFVLEGEvTLTLGGE--THELT--PGGYAYLPPGTPWTLRNAGDEPA 127

gentisate 1,2-dioxygenase, 1-hydroxy-2-naphthoate dioxygenase, and salicylate 1,2-dioxygenase, N-terminal cupin domain; This family includes the N-terminal cupin domains of three closely related bicupin aromatic ring-cleaving dioxygenases: gentisate 1,2-dioxygenase (GDO), salicylate 1,2-dioxygenase (SDO), and 1-hydroxy-2-naphthoate dioxygenase (NDO). GDO catalyzes the cleavage of the gentisate (2,5-dihydroxybenzoate) aromatic ring, a key step in the gentisate degradation pathway allowing soil bacteria to utilize 2,5-xylenol, 3,5-xylenol, and m-cresol as sole carbon and energy sources. NDO catalyzes the cleavage of 1-hydroxy-2-naphthoate as part of the bacterial phenanthrene degradation pathway. SDO is a ring cleavage dioxygenase from Pseudaminobacter salicylatoxidans that oxidizes salicylate to 2-oxohepta-3,5-dienedioic acid via a novel ring fission mechanism. SDO differs from other known GDOs and NDOs in its unique ability to oxidatively cleave many different salicylate, gentisate and 1-hydroxy-2-naphthoate substrates with high catalytic efficiency. The active site of these enzymes is located in the N-terminal domain but could be influenced by changes in the C-terminal domain, which lacks the strictly conserved metal-binding residues found in other cupin domains and is thought to be an inactive vestigial remnant.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 488811425  39 LLTIPPGGRARAHKHASheTAI-YVLEGE---TVMFwGErlehRMEVGAGELLYIPADMPHLPMNLSDRPAV 106
Cdd:cd02216   25 LQLLPPGEVAPAHRHTP--NALrFVLEGPgayTTVD-GE----RCDMEPGDLILTPPGTWHDHGNEGDEPAI 89