An updated structural classification of substrate‐binding proteins

Abstract

Substrate-binding proteins (SBPs) play an important role in solute uptake and signal transduction. In 2010, Berntsson et al. classified the 114 organism-specific SBP structures available at that time and defined six protein clusters, based on their structural similarity. Since then, the number of unique SBP structures has increased almost fivefold, whereas the number of protein entries in the Protein Data Bank (PDB) nearly doubled. On the basis of the much larger dataset, we now subclassify the SBPs within the original clusters. Moreover, we propose a 7th cluster based on a small group of SBPs with structural features significantly different from those observed in the other proteins.

Crystal Structure of the Substrate-Binding Domain from Listeria monocytogenes Bile-Resistance Determinant BilE

“…Each domain is comprised of a five-stranded β-sheet surrounded by α-helices. This fold is characteristic of SBPs of subcluster F-III [26,27]. As expected based on sequence similarity, a search for structural homologs in the PDB using the Dali server [50] gave the best match as the open, unliganded structure of AfProX (PDB ID 1SW5, Table A3).…”

“…Our final list of 198 sequences contains proteins with various domain organizations including isolated SBPs as well as TMD-SBD, SBD-TMD and even SBD-SBD fusions ( Figure 4A, Supplementary File S1). Analysis with HHpred [36] suggests that these additional C-terminal SBDs belong to structural subclusters F-IV or E-II, both of which contain SBPs that bind amino acids and are associated with importers, channels or receptors [26,27]. We also identified three SBPs and four TMD-SBD fusions which contain a sequence swap similar to OpuAC from Bacillus subtilis [39,40] (Figure 4A).…”

“…We also identified three SBPs and four TMD-SBD fusions which contain a sequence swap similar to OpuAC from Bacillus subtilis [39,40] (Figure 4A). additional C-terminal SBDs belong to structural subclusters F-IV or E-II, both of which contain SBPs that bind amino acids and are associated with importers, channels or receptors [26,27]. We also identified three SBPs and four TMD-SBD fusions which contain a sequence swap similar to OpuAC from Bacillus subtilis [39,40] ( Figure 4A).…”

“…Based on sequence homology, the C-terminus of BilEB contains a substrate-binding domain (SBD) belonging to substrate-binding protein (SBP) subcluster F-III [26,27]. All characterized members of this cluster are part of an ABC transporter and bind QACs via cation-π interactions.…”

“…The soluble C-terminal domain of BilEB was crystallized and confirmed to have a substrate-binding protein fold belonging to structural subcluster F-III [26,27]. The characterized members of this group are all associated with ABC importers and bind compatible solutes.…”