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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442618894   405 GKLKLSGIEYEMVQTIAERLHVSIEMQgeNSNLYHLFQQLIDGEIEMIVGGIDEDPSISQFVSSSIPYHQDE 476
Cdd:smart00062  18 EDGELTGFDVDLAKAIAKELGLKVEFV--EVSFDSLLTALKSGKIDVVAAGMTITPERAKQVDFSDPYYRSG 87

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442618894   405 GKLKLSGIEYEMVQTIAERLHVSIEMQgeNSNLYHLFQQLIDGEIEMIVGGIDEDPSISQFVSSSIPYHQDE 476
Cdd:smart00062  18 EDGELTGFDVDLAKAIAKELGLKVEFV--EVSFDSLLTALKSGKIDVVAAGMTITPERAKQVDFSDPYYRSG 87

membrane-bound lytic murein transglycosylase MltF;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 442618894 410 SGIEYEMVQTIAERLHVSIEMQgENSNLYHLFQQLIDGEIEMIVGGIDEDPSISQFVSSSIPYHQ 474
Cdd:PRK10859  64 TGFEYELAKRFADYLGVKLEIK-VRDNISQLFDALDKGKADLAAAGLTYTPERLKQFRFGPPYYS 127

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 442618894  408 KLSGIEYEMVQTIAERLHVSIEMQ-GENSNlyhLFQQLIDGEIEMIVGGIDEDPSISQFVSSSIPY 472
Cdd:pfam00497  20 KLVGFDVDLAKAIAKRLGVKVEFVpVSWDG---LIPALQSGKVDLIIAGMTITPERAKQVDFSDPY 82

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442618894   405 GKLKLSGIEYEMVQTIAERLHVSIEMQgeNSNLYHLFQQLIDGEIEMIVGGIDEDPSISQFVSSSIPYHQDE 476
Cdd:smart00062  18 EDGELTGFDVDLAKAIAKELGLKVEFV--EVSFDSLLTALKSGKIDVVAAGMTITPERAKQVDFSDPYYRSG 87

ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 442618894 408 KLSGIEYEMVQTIAERLHVSIEMQGENSNlyHLFQQLIDGEIEMIVGGIDEDPSISQFVSSSIPYHQDELTWCVAR 483
Cdd:COG0834   20 KLVGFDVDLARAIAKRLGLKVEFVPVPWD--RLIPALQSGKVDLIIAGMTITPEREKQVDFSDPYYTSGQVLLVRK 93

The solute binding domain of YfhD proteins, a member of the type 2 periplasmic binding fold protein superfamily; This subfamily includes the solute binding domain YfhD_N. These domains are found in the YfhD proteins that are predicted to function as lytic transglycosylases that cleave the glycosidic bond between N-acetylmuramic acid and N-acetylglucosamin in peptidoglycan, while the YfhD_N domain might act as an auxiliary or regulatory subunit. In addition to periplasmic solute binding domain, they have an SLT domain, typically found in soluble lytic transglycosylases, and a C-terminal low complexity domain. The YfhD proteins might have been recruited to create localized cell wall openings required for transport of large substrates such as DNA. They 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 442618894 408 KLSGIEYEMVQTIAERLHVSIEMQgENSNLYHLFQQLIDGEIEMIVGGIDEDPSISQFVSSSIPYHQD 475
Cdd:cd01009   20 GPRGFEYELAKAFADYLGVELEIV-PADNLEELLEALEEGKGDLAAAGLTITPERKKKVDFSFPYYYV 86