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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2498035512   1 MLPYLIKNA-NLPLRTGALLAGtklEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWLG 63
Cdd:cd13712   159 AANYLVKTSlELPPTGGAFARQ---KSGIPFRKGNPKLKAAINKAIEDLRADGTLAKLSEKWFG 219

Substrate binding domain of an Escherichia coli ABC transporter; the type 2 periplasmic binding protein fold; This group contains cystine binding domain FliY and its related proteins. Cystine is an oxidized dimeric form of cysteine that is required for optimal bacterial growth. In Bacillus subtilis, three ABC transporters, TcyJKLMN (YtmJKLMN), TcyABC (YckKJI), and YxeMNO are involved in uptake of cystine. Likewise, three uptake systems were identified in Salmonella enterica serovar Typhimurium, while in Escherichia coli, two transport systems seem to be involved in cystine uptake. Moreover, L-cystine limitation was shown to prevent virulence of Neisseria gonorrhoeae; thus, its L-cystine solute receptor (Ngo0372) may be suited as target for an antimicrobial vaccine. The cystine receptor belongs to the type 2 periplasmic binding fold protein superfamily (PBP2). The PBP2 proteins 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. 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 receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2498035512   1 MLPYLIKNA-NLPLRTGALLAGtklEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWLG 63
Cdd:cd13712   159 AANYLVKTSlELPPTGGAFARQ---KSGIPFRKGNPKLKAAINKAIEDLRADGTLAKLSEKWFG 219

Bacterial extracellular solute-binding proteins, family 3; This is a sensor domain found in solute-binding protein family 3 members from Gram-positive bacteria, Gram-negative bacteria and archaea. It can also be found in the N-terminal of the membrane-bound lytic murein transglycosylase F (MltF) protein. This domain recognizes Nicotinate, quidalnate, pyridine-2,5-dicarboxylate and salicylate (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2498035512   1 MLPYLIKNANLPLRTGALLAGTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWL 62
Cdd:pfam00497 160 VAAYLIKKNPGLNLVVVGEPLSPEPYGIAVRKGDPELLAAVNKALAELKADGTLAKIYEKWF 221

Bacterial periplasmic substrate-binding proteins; bacterial proteins, eukaryotic ones are in PBPe

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2498035512    4 YLIKNANLPLRTGALLAGTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWL 62
Cdd:smart00062 161 LVKQHGLPELKIVPDPLDTPEGYAIAVRKGDPELLDKINKALKELKADGTLKKISEKWF 219

Substrate binding domain of an Escherichia coli ABC transporter; the type 2 periplasmic binding protein fold; This group contains cystine binding domain FliY and its related proteins. Cystine is an oxidized dimeric form of cysteine that is required for optimal bacterial growth. In Bacillus subtilis, three ABC transporters, TcyJKLMN (YtmJKLMN), TcyABC (YckKJI), and YxeMNO are involved in uptake of cystine. Likewise, three uptake systems were identified in Salmonella enterica serovar Typhimurium, while in Escherichia coli, two transport systems seem to be involved in cystine uptake. Moreover, L-cystine limitation was shown to prevent virulence of Neisseria gonorrhoeae; thus, its L-cystine solute receptor (Ngo0372) may be suited as target for an antimicrobial vaccine. The cystine receptor belongs to the type 2 periplasmic binding fold protein superfamily (PBP2). The PBP2 proteins 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. 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 receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2498035512   1 MLPYLIKNA-NLPLRTGALLAGtklEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWLG 63
Cdd:cd13712   159 AANYLVKTSlELPPTGGAFARQ---KSGIPFRKGNPKLKAAINKAIEDLRADGTLAKLSEKWFG 219

cystine ABC transporter substrate-binding protein;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2498035512  20 AGTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWLGTDASQ 68
Cdd:PRK11260  218 AFSRQESGVALRKGNPDLLKAVNQAIAEMQKDGTLKALSEKWFGADVTK 266

Substrate binding domain of ABC transporters involved in cystine import; the type 2 periplasmic binding protein fold; This subgroup includes cystine-binding domain of periplasmic receptor-dependent ATP-binding cassette transporters from Neisseria gonorrhoeae and Bacillus subtilis and their related proteins. Cystine is an oxidized dimeric form of cysteine that is required for optimal bacterial growth. In Bacillus subtilis, three ABC transporters, TcyJKLMN (YtmJKLMN), TcyABC (YckKJI), and YxeMNO are involved in uptake of cystine. Likewise, three uptake systems were identified in Salmonella enterica serovar Typhimurium, while in Escherichia coli, two transport systems seem to be involved in cystine uptake. Moreover, L-cystine limitation was shown to prevent virulence of Neisseria gonorrhoeae; thus, its L-cystine solute receptor (Ngo0372) may be suited as target for an antimicrobial vaccine. The cystine receptor belongs to the type 2 periplasmic binding fold protein superfamily (PBP2). The PBP2 proteins 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. 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 receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2498035512   2 LPYLIKNANLPLRTGALlAGTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWLGTD 65
Cdd:cd13711   159 LDYKKQHPDAPVKIAAE-TDDASESAFLVRKGNDELVAAINKALKELKADGTLKKISEKYFGKD 221

Bacterial extracellular solute-binding proteins, family 3; This is a sensor domain found in solute-binding protein family 3 members from Gram-positive bacteria, Gram-negative bacteria and archaea. It can also be found in the N-terminal of the membrane-bound lytic murein transglycosylase F (MltF) protein. This domain recognizes Nicotinate, quidalnate, pyridine-2,5-dicarboxylate and salicylate (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2498035512   1 MLPYLIKNANLPLRTGALLAGTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWL 62
Cdd:pfam00497 160 VAAYLIKKNPGLNLVVVGEPLSPEPYGIAVRKGDPELLAAVNKALAELKADGTLAKIYEKWF 221

Substrate binding domain of an ABC transporter TcyJKLMN; the type 2 periplasmic binding protein fold; This group contains periplasmic cystine-binding domain (TcyK) of an ATP-binding cassette transporter from Bacillus subtilus and its closely related proteins. Cystine is an oxidized dimeric form of cysteine that is required for optimal bacterial growth. In Bacillus subtilis, three ABC transporters, TcyJKLMN (YtmJKLMN), TcyABC (YckKJI), and YxeMNO are involved in uptake of cystine. Likewise, three uptake systems were identified in Salmonella enterica serovar Typhimurium, while in Escherichia coli, two transport systems seem to be involved in cystine uptake. Moreover, L-cystine limitation was shown to prevent virulence of Neisseria gonorrhoeae; thus, its L-cystine solute receptor (Ngo0372) may be suited as target for an antimicrobial vaccine. The cystine receptor belongs to the type 2 periplasmic binding fold protein superfamily (PBP2). The PBP2 proteins 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. 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 receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2498035512   4 YLIKNANLPLRTGALLAGTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWLGTD 65
Cdd:cd13710   170 TIIKTQGDNLKVVDLPPVKKPYVYFLFNKDQQKLQKDIDKALKELKKDGTLKKLSKKYFGGD 231

Peptide-binding protein and related homologs; type 2 periplasmic binding protein fold; This domain is found in solute binding proteins that serve as initial receptors in the ABC transport, signal transduction and channel gating. The PBP2 proteins share the same architecture as periplasmic binding proteins type 1, 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 majority of PBP2 proteins function in the uptake of small soluble substrates in eubacteria and archaea. 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2498035512   4 YLIKNANLPLRTgALLAGTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEW 61
Cdd:cd13530   161 YYVKKNGPDLKV-VGEPLTPEPYGIAVRKGNPELLDAINKALAELKADGTLDKLLEKW 217

Polar amino acids-binding domain of ATP-binding cassette transporter-like systems that belong to the type 2 periplasmic binding fold protein superfamily; This subfamily includes periplasmic binding domain of ATP-binding cassette transporter-like systems that serve as initial receptors in the ABC transport of amino acids and their derivatives in eubacteria. 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. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. The Abp proteins belong to the PBPI 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
                  ....*....|....*....|....*....|....*....
gi 2498035512  25 EMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWLG 63
Cdd:cd00996   189 EYGVGFRKEDTELKEKINKALDEMKADGTAAKISQKWFG 227

Substrate binding domain of ABC-type octopine transporter-like; the type 2 periplasmic-binding protein fold; This group includes periplasmic octopine-binding protein and related proteins. This group belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. PBP2 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. 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 receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2498035512   3 PYLIKNANLPLRTGALLAGTKLE-------MGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEW 61
Cdd:cd13699   145 TYLAAFLAKPDNADLTLVGPKLSgdiwgegEGVGLRKGDTELKAKFDSAIKAAVADGTVKKLSEKW 210

Substrate-binding domain of cysteine- and aspartate/glutamate-binding proteins; the type 2 periplasmic-binding protein fold; This family comprises of the periplasmic-binding protein component of ABC transporters specific for cysteine and carboxylic amino acids, as well as their closely related proteins. The cysteine and aspartate-glutamate binding domains belong to the type 2 periplasmic binding protein fold superfamily (PBP2), whose many members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. The PBP2 proteins 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. 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 receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2498035512  21 GTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWL 62
Cdd:cd01000   187 FSQEPYGIAVRKGDTELLKAVNATIAKLKADGELAEIYKKWL 228

Substrate binding domain of ABC glutamine transporter from Bacillus subtilis; the type 2 periplasmic-bindig protein fold; This group includes periplasmic glutamine-binding domain GlnP from Bacillus subtilis and its related proteins. The GlnP domain belongs to the type 2 periplasmic binding protein fold superfamily (PBP2), whose many members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. The PBP2 proteins 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. 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 receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2498035512  26 MGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWLG 63
Cdd:cd13689   192 YGIGVPKGESALRDFVNETLADLEKDGEADKIYDKWFG 229

The solute binding domain of ArtJ protein, a member of the type 2 periplasmic binding fold protein superfamily; An arginine-binding protein found in Chlamydiae trachomatis (CT-ArtJ) and pneumoniae (CPn-ArtJ) and its closely related proteins. CT- and CPn-ArtJ are shown to have different immunogenic properties despite a high sequence similarity. The ArtJ proteins display the type 2 periplasmic binding fold organized in two alpha-beta domains with arginine-binding region at their interface.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2498035512  19 LAGTKLEMGIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEW 61
Cdd:cd00999   181 LPEWGLGKALAVAKDDPALKEAVNKALDELKKEGELAALRKKW 223

Substrate-binding domain of ABC aspartate-glutamate transporter; the type 2 periplasmic binding protein fold; This subfamily represents the periplasmic-binding protein component of ABC transporter specific for carboxylic amino acids, including GtlI from Escherichia coli. The aspartate-glutamate binding domain belongs to the type 2 periplasmic binding protein fold superfamily (PBP2), whose many members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. The PBP2 proteins 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. 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 receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 2498035512  27 GIPYRKGNPKFAKAIDDALIALQQDGTLRKLSIEWL 62
Cdd:cd13688   203 GLMLRKDDPDFRLLVDRALAQLYQSGEIEKLYDKWF 238