Type 2 periplasmic binding fold superfamily; This evolutionary model and hierarchy represent the ligand-binding domains found in solute binding proteins that serve as initial receptors in the transport, signal transduction and channel gating. The PBP2 proteins share the same architecture as periplasmic binding proteins type 1 (PBP1), but have a different topology. They are typically comprised of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. The origin of PBP module can be traced across the distant phyla, including eukaryotes, archebacteria, and prokaryotes. The majority of PBP2 proteins are involved in the uptake of a variety of soluble substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the family includes ionotropic glutamate receptors and unorthodox sensor proteins involved in signal transduction. The substrate binding domain of the LysR transcriptional regulators and the oligopeptide-like transport systems also contain the type 2 periplasmic binding fold and thus they are significantly homologous to that of the PBP2; however, these two families are grouped into a separate hierarchy of the PBP2 superfamily due to the large number of protein sequences.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768753374   5 KITFLLNWQPTPYHIPIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSVASLL 84
Cdd:cd13650    1 KITFLLNWHATPYHIPIFLAQTKGYFKEEGLDVAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSIGSLL 80

                         90       100
                 ....*....|....*....|....
gi 768753374  85 DEPFTGVLYLKGSGITEDFQSLKG 108
Cdd:cd13650   81 DEPFTGVIYLKGSGITEDFQSLKG 104

Substrate binding domain of ABC-type transporters for thiamin biosynthetic pathway intermediates; a member of the type 2 periplasmic binding fold superfamily; ThiY is the periplasmic N-formyl-4-amino-5-(aminomethyl)-2-methylpyrimidine (FAMP) binding component of the ABC transport system (ThiXYZ). FAMP is imported into cell by the transporter, where it is then incorporated into the thiamin biosynthetic pathway. The closest structural homologs of ThiY are periplasmic binding proteins involved in alkanesulfonate/nitrate and bicarbonate transport , as well as THI5 which is responsible for the synthesis of 4-amino-5-(hydroxymethyl)-2-methylpyrimidine phosphate (HMP-P) in the thiamin biosynthetic pathway of eukaryotes. After binding the ligand, they interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. The ThiY/THI5 proteins belong to the PBP2 superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768753374   5 KITFLLNWQPTPYHIPIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSVASLL 84
Cdd:cd13650    1 KITFLLNWHATPYHIPIFLAQTKGYFKEEGLDVAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSIGSLL 80

                         90       100
                 ....*....|....*....|....
gi 768753374  85 DEPFTGVLYLKGSGITEDFQSLKG 108
Cdd:cd13650   81 DEPFTGVIYLKGSGITEDFQSLKG 104

ABC-type nitrate/sulfonate/bicarbonate transport system, periplasmic component [Inorganic ion transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768753374   2 STDKITFLLNWQPTPYHIPIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSVA 81
Cdd:COG0715   18 AAEKVTLRLGWLPNTDHAPLYVAKEKGYFKKEGLDVELVEFAGGAAALEALAAGQADFGVAGAPPALAARAKGAPVKAVA 97

                         90       100
                 ....*....|....*....|....*..
gi 768753374  82 SLLDEPFTGVLYLKGSGITeDFQSLKG 108
Cdd:COG0715   98 ALSQSGGNALVVRKDSGIK-SLADLKG 123

Substrate binding domain of ABC-type transporters for thiamin biosynthetic pathway intermediates; a member of the type 2 periplasmic binding fold superfamily; ThiY is the periplasmic N-formyl-4-amino-5-(aminomethyl)-2-methylpyrimidine (FAMP) binding component of the ABC transport system (ThiXYZ). FAMP is imported into cell by the transporter, where it is then incorporated into the thiamin biosynthetic pathway. The closest structural homologs of ThiY are periplasmic binding proteins involved in alkanesulfonate/nitrate and bicarbonate transport , as well as THI5 which is responsible for the synthesis of 4-amino-5-(hydroxymethyl)-2-methylpyrimidine phosphate (HMP-P) in the thiamin biosynthetic pathway of eukaryotes. After binding the ligand, they interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. The ThiY/THI5 proteins belong to the PBP2 superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768753374   5 KITFLLNWQPTPYHIPIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSVASLL 84
Cdd:cd13650    1 KITFLLNWHATPYHIPIFLAQTKGYFKEEGLDVAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSIGSLL 80

                         90       100
                 ....*....|....*....|....
gi 768753374  85 DEPFTGVLYLKGSGITEDFQSLKG 108
Cdd:cd13650   81 DEPFTGVIYLKGSGITEDFQSLKG 104

NMT1/THI5 like; This family contains the NMT1 and THI5 proteins. These proteins are proposed to be required for the biosynthesis of the pyrimidine moiety of thiamine.3]. They are regulated by thiamine. The protein adopts a fold related to the periplasmic binding protein (PBP) family. Both pyridoxal-5'-phosphate (PLP) and an iron atom are bound to the protein suggesting numerous residues of the active site necessary for HMP-P biosynthesis. The yeast protein is a dimer and, although exceptionally using PLP as a substrate, has notable similarities with enzymes dependent on this molecule as a cofactor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768753374   16 PYHIPIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSVASLLDEPFTGVLYLK 95
Cdd:pfam09084   2 PNHAGLYVAQEKGYFKEEGLDVEIVEPADPSDATQLVASGKADFGVSYQESVLLARAKGLPVVSVAALIQHPLSGVISLK 81

                          90
                  ....*....|...
gi 768753374   96 GSGItEDFQSLKG 108
Cdd:pfam09084  82 DSGI-KSPKDLKG 93

ABC-type nitrate/sulfonate/bicarbonate transport system, periplasmic component [Inorganic ion transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768753374   2 STDKITFLLNWQPTPYHIPIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMGLKAMIHTLAAKARGFPVTSVA 81
Cdd:COG0715   18 AAEKVTLRLGWLPNTDHAPLYVAKEKGYFKKEGLDVELVEFAGGAAALEALAAGQADFGVAGAPPALAARAKGAPVKAVA 97

                         90       100
                 ....*....|....*....|....*..
gi 768753374  82 SLLDEPFTGVLYLKGSGITeDFQSLKG 108
Cdd:COG0715   98 ALSQSGGNALVVRKDSGIK-SLADLKG 123

Putative substrate binding domain of an ABC-type transporter similar to ThiY/THI5; the type 2 periplasmic binding protein fold; This subfamily is phylogenetically similar to ThiY, which is the periplasmic N-formyl-4-amino-5-(aminomethyl)-2-methylpyrimidine (FAMP) binding component of the ABC transport system (ThiXYZ). FAMP is imported into cell by the transporter, where it is then incorporated into the thiamin biosynthetic pathway. The closest structural homologs of ThiY are THI5, which is responsible for the synthesis of 4-amino-5-(hydroxymethyl)-2-methylpyrimidine phosphate (HMP-P) in the thiamin biosynthetic pathway of eukaryotes, and periplasmic binding proteins involved in alkanesulfonate/nitrate and bicarbonate transport. After binding the ligand, they interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. The ThiY/THI5 proteins belong to the PBP2 superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768753374  20 PIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMGLKA-MIHTLAAKARGFPVTSVASLLDEP----FTGVLYL 94
Cdd:cd13652   16 PVYIAAEKGYFKEEGLDVEITRFASGAEILAALASGQVDVAGSSpGASLLGALARGADLKIVAEGLGTTpgygPFAIVVR 95

                 ....*.
gi 768753374  95 KGSGIT 100
Cdd:cd13652   96 ADSGIT 101

Substrate binding domain of ABC-type nitrate/bicarbonate transporters, a member of the type 2 periplasmic binding fold superfamily; This subfamily includes nitrate (NrtA) and bicarbonate (CmpA) receptors. These domains are found in eubacterial perisplamic-binding proteins that serve as initial receptors in the ABC transport of bicarbonate, nitrate, taurine, or a wide range of aliphatic sulfonates, while other closest homologs are involved in thiamine (vitamin B1) biosynthetic pathway and desulfurization (DszB). After binding their ligand with high affinity, they interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. These binding proteins belong to the PBP2 superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768753374  18 HIPIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMG--LKAMIHtLAAKARGFPVTSVASL 83
Cdd:cd13553   12 HAPLLVAKEKGFFEKEGLDVELVKFPSWADLRDALAAGELDAAhvLAPMPA-AATYGKGAPIKVVAGL 78

Putative substrate binding domain of sulfonate binding protein-like, the type 2 periplasmic binding protein fold; This subfamily includes the periplasmic component of putative ABC-type sulfonate transport system similar to SsuA. These domains are found in eubacterial SsuA proteins that serve as initial receptors in the ABC transport of bicarbonate, nitrate, taurine, or a wide range of aliphatic sulfonates, while other closest homologs are involved in thiamine (vitamin B1) biosynthetic pathway and desulfurization (DszB). After binding the ligand, SsuA interacts with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. The SsuA proteins belong to the PBP2 superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768753374  11 NWQPTPY-HIPIFLAQTKGYFKEQGLDIAILEPTNPSDVTELIGSGKVDMG-LKAMIHTLAAKaRGFPVTSVaSLLDEPF 88
Cdd:cd13561    5 GYLPALAvAGPIFIAKEKGLFAKHGLDPDFIEFTSGPPLVAALGSGSLDVGyTGPVAFNLPAS-GQAKVVLI-NNLENAT 82

                         90       100
                 ....*....|....*....|
gi 768753374  89 TGVLYLKGSGITeDFQSLKG 108
Cdd:cd13561   83 ASLIVRADSGIA-SIADLKG 101