Identifying ligand-binding specificity of the oligopeptide receptor OppA from Bifidobacterium longum KACC91563 by Structure-based molecular modeling

Abstract

Background: The OppA receptor as a ATP-binding cassette (ABC) transporter plays key roles in protecting host organism and transport nutrients across the intestine by the oligopeptide transporter from symbiotic bacteria directs maturation of the host immune system. Among lactic acid bacteria, Bifidobacterium longum KACC91563, isolated from fecal samples of healthy Korean neonates, has the capability to alleviate food allergy effects. The extracellular OppA receptor from gram-positive Bifidobacterium longum KACC91563 translocate nutrients-peptides from the outside environment of intestinal tract to the inside of the symbiotic cell, as a peptide importer. Hence, it was attempting to explicate the relationship between the substrate’s specificity from the OppA importer and the probiotic effects of B. logum KACC91563 in the host intestine. The probiotic effects of B. logum KACC91563 were attributed to the enhancement of the epithelial barrier by several different strain sepcific ways to prevent the strong adhesion of pathogens. The specialized structure-function relationship from the OppA importer could provide the abstract of substrate specificity into unique immunological properties of that the host organism.Results: In the study, we characterized the extracellular OppA importer from B. longum KACC91563 of intestinal microbiome by various protein structure-based modelings in silico. Structural characterization by conserved 5 patches and 4 functional motifs from specific trace residues of the OppA importer. The hydrate surface of the binding site had been decipted by specific trace residues of the OppA that trace residues of Thr58, Lys185, Trp443, and Tyr447, which were characterized in highly exposed hydrophobic binding pocket by its aggregation prones. Therefore, the spatial aggregation propensity in the binding site of the extracellular OppA importer plays a vital role in the specific interaction determinant for peptide binding. In addition, alanine mutation energy values allowed for the virtual determination of the relationships between the energy effects of the peptide binding site mutation on the transporter structural stability, the peptide binding affinity, and the transporter-related peptide substrate selectivity from OppA importer. In particular, distinctive seven pharmacophoric features comprised of two H-bonding donor(P1), three H-bonding acceptor(P8), and two hydrophobic points (P5 and P8) matched the the OppA receptor-peptide ligand interactions within their binding pocket structure. There are distinct interactions to fix the positions of the N(P1) and C(P8) termini of the complex of OppA-peptide from B. longum KACC91563 such as side chain-specific interactions with the OppA, compared to that of the Lactococcus latis (L. lactics) OppA.Conclusions: The specialized structure-function relationship from the OppA import could provide the abstract of substrate specificity into unique immunological properties of the host organism by stucutre-based molecular modeling. In the current study, we attempted explication of the relationship between the substrate’s specificity from the OppA importer and the probiotic effects of B. longum KACC91563 in the host intestine based on the structure-function perspectives of the OppA importer. Moreover, functional characterization of solute-binding proteins (such as 15 cell wall proteins and 20 extracellular proteins) on the B. longum KACC91563 genome will lead to insight of key switch for substate’s metabolism into reprogramming immune responses in the host intestine.