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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 389886435  43 LAVRPDfefrDDMLDTSVVVSHPSPINLIKYFTRK---DVRFKLVNSTSQAARKVKEGLYDI-ALTNELARQKYGLTFVK 118
Cdd:cd13633   89 LLVRPG----VDLSDITKVYSHPQALAQCRQFLRRnlpGAELEYTGSTAEAARLVAESPEGWaAIGTLRAAELYGLEILA 164

                 .
gi 389886435 119 T 119
Cdd:cd13633  165 E 165

Catalytic domain of prephenate dehydratase from Staphylococcus aureus and similar proteins, subgroup 4; the type 2 periplasmic binding protein fold; Prephenate dehydratase (PDT, EC:4.2.1.51) converts prephenate to phenylpyruvate through dehydration and decarboxylation reactions. PDT plays a key role in the biosynthesis of L-Phe in organisms that utilize the shikimate pathway. PDT is allosterically regulated by L-Phe and other amino acids. The catalytic PDT domain consists of two similar subdomains with a cleft in between, which hosts the highly conserved active site. In gram-postive bacteria and archaea, PDT is a monofunctional enzyme, consisting of a catalytic domain (PDT domain) and a regulatory domain (ACT) (aspartokinase, chorismate mustase domain). In gram-negative bacteria, PDT exists as fusion protein with chorismate mutase (CM), forming a bifunctional enzyme, P-protein (PheA). The CM in the P-protein catalyzes the pericycle isomerization of chorismate to prephenate that serves as a substrate for PDT. The CM and PDT are essentail enzymes for the biosynthesis of aromatic amino acids in microorganisms but are not found in humans. Thus, both CM and PDT can potentially serve as drug targets against microbial pathogens. The PDT domain has the same structural fold as the type 2 periplasmic binding proteins (PBP2), many of which 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 389886435  43 LAVRPDfefrDDMLDTSVVVSHPSPINLIKYFTRK---DVRFKLVNSTSQAARKVKEGLYDI-ALTNELARQKYGLTFVK 118
Cdd:cd13633   89 LLVRPG----VDLSDITKVYSHPQALAQCRQFLRRnlpGAELEYTGSTAEAARLVAESPEGWaAIGTLRAAELYGLEILA 164

                 .
gi 389886435 119 T 119
Cdd:cd13633  165 E 165

prephenate dehydratase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 389886435  61 VVSHPSPINLIKYFTRK---DVRFKLVNSTSQAARKVKEGLYDI--ALTNELARQKYGLTFVKT 119
Cdd:PRK11898 103 VYSHPQALAQCRKWLAEhlpGAELEPANSTAAAAQYVAEHPDEPiaAIASELAAELYGLEILAE 166

Catalytic domain of prephenate dehydratase from Staphylococcus aureus and similar proteins, subgroup 4; the type 2 periplasmic binding protein fold; Prephenate dehydratase (PDT, EC:4.2.1.51) converts prephenate to phenylpyruvate through dehydration and decarboxylation reactions. PDT plays a key role in the biosynthesis of L-Phe in organisms that utilize the shikimate pathway. PDT is allosterically regulated by L-Phe and other amino acids. The catalytic PDT domain consists of two similar subdomains with a cleft in between, which hosts the highly conserved active site. In gram-postive bacteria and archaea, PDT is a monofunctional enzyme, consisting of a catalytic domain (PDT domain) and a regulatory domain (ACT) (aspartokinase, chorismate mustase domain). In gram-negative bacteria, PDT exists as fusion protein with chorismate mutase (CM), forming a bifunctional enzyme, P-protein (PheA). The CM in the P-protein catalyzes the pericycle isomerization of chorismate to prephenate that serves as a substrate for PDT. The CM and PDT are essentail enzymes for the biosynthesis of aromatic amino acids in microorganisms but are not found in humans. Thus, both CM and PDT can potentially serve as drug targets against microbial pathogens. The PDT domain has the same structural fold as the type 2 periplasmic binding proteins (PBP2), many of which 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 389886435  43 LAVRPDfefrDDMLDTSVVVSHPSPINLIKYFTRK---DVRFKLVNSTSQAARKVKEGLYDI-ALTNELARQKYGLTFVK 118
Cdd:cd13633   89 LLVRPG----VDLSDITKVYSHPQALAQCRQFLRRnlpGAELEYTGSTAEAARLVAESPEGWaAIGTLRAAELYGLEILA 164

                 .
gi 389886435 119 T 119
Cdd:cd13633  165 E 165

Catalytic domain of prephenate dehydratase from Arthrobacter aurescens and similar proteins, subgroup 3; the type 2 periplasmic binding protein fold; Prephenate dehydratase (PDT, EC:4.2.1.51) converts prephenate to phenylpyruvate through dehydration and decarboxylation reactions. PDT plays a key role in the biosynthesis of L-Phe in organisms that utilize the shikimate pathway. PDT is allosterically regulated by L-Phe and other amino acids. The catalytic PDT domain consists of two similar subdomains with a cleft in between, which hosts the highly conserved active site. In gram-postive bacteria and archaea, PDT is a monofunctional enzyme, consisting of a catalytic domain (PDT domain) and a regulatory domain (ACT) (aspartokinase, chorismate mustase domain). In gram-negative bacteria, PDT exists as fusion protein with chorismate mutase (CM), forming a bifunctional enzyme, P-protein (PheA). The CM in the P-protein catalyzes the pericycle isomerization of chorismate to prephenate that serves as a substrate for PDT. The CM and PDT are essentail enzymes for the biosynthesis of aromatic amino acids in microorganisms but are not found in humans. Thus, both CM and PDT can potentially serve as drug targets against microbial pathogens. The PDT domain has the same structural fold as the type 2 periplasmic binding proteins (PBP2), many of which 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 389886435  43 LAVRPDfefrDDMLDTSVVVSHPSPINLIKYFTRK---DVRFKLVNSTSQAARKVKEGLYDIALTNELARQKYGLT 115
Cdd:cd13632   89 LAVRPG----TTLADVRTVATHPHALAQCRGWLAEnlpGAEFVPASSNAAAARDVAEGEYDAALAPPIAAELYGLE 160