Oligopeptide-binding protein from nontypeable Haemophilus influenzae has ligand-specific sites to accommodate peptides and heme in the binding pocket

Abstract

by guest on July 10, 2020 http://www.jbc.org/ Downloaded from Figure 1. Crystal structure of nthiOppA in closed ligand-bound conformation. A, crystal structure of nthiOppA, colored by domain (I A , salmon; I B , wheat; II, cyan), bound to co-purified peptide in green. Inset, surface and stick representation of the co-purified peptide in substrate-binding pocket. B, cartoon representation of the ligand-bound structure of nthiOppA aligned with the open unbound ecOppA structure in gray (PDB code 3TCH), and surface representation of cross-sections of ecOppA and nthiOppA. Based on the alignment with nthiOppA, the green spheres in the open unbound ecOppA structure highlight the binding site where peptide interacts with the SBP to form the closed conformation.

Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner

“…For HbpA, the suggested site is supported by what has been previously predicted [89] and corresponds well to a very recent study where heme was docked to HpHbpA, OppA from H. influenzae (HiOppA) and NikA from E. coli (EcNikA) [90]. In the latter study, heme was suggested to bind in a site that was distinct but close to the site for other ligands (glutathione for HpHbpA, peptide for HiOppA, and butane-1,2,4-tricarboxylate-chelated nickel for EcNikA) and the ability of bind heme and other ligands simultaneously was demonstrated using surface plasmon resonance.…”

“…In NTHi, four Cluster C proteins with capability to bind heme have been identified: HbpA, SapA, and OppA, which bind hydrophobic oligopeptides, and NTHI0310 with an unknown canonical substrate specificity. These proteins present overlapping functionality and multisubstrate specificity [90]. This may not be exclusive to NTHi given that the E. coli Cluster C nickel SBP NikA binds heme and plays a role as a heme chaperone in the periplasm [111].…”

Transcriptional response to metal starvation in the emerging pathogen Mycoplasma genitalium is mediated by Fur-dependent and –independent regulatory pathways

“…Oligopeptide and dipeptide permeases have been found to be significantly up-regulated during iron starvation in other pathogenic bacteria [12,38] and they have been implicated in metal acquisition in S. aureus [39] and E. coli [40]. Moreover, some oligopeptide-binding proteins can accommodate haeme in its binding pocket [41], hence providing a new strategy to acquire iron from the host. In addition, the oligopeptide transport ATP-binding protein OppD has been shown to be critical for survival of the avian pathogen Mycoplasma gallisepticum within the respiratory tract [42], supporting the relevance of oligopeptide permeases in mycoplasma infection.…”

Bacterial ABC transporters of iron containing compounds

“…The RdKW20 strain (an avirulent d serotype strain, devoid of capsule) was the first completely sequenced bacterial genome and has been used in many studies. It expresses many different heme/hemoprotein receptors, and there are several reports of periplasmic heme-binding proteins [59,72] A, also named HI0853 in RdKW20) was the first periplasmic heme binding protein reported in this organism [73,74]. It was identified in the Hib strain DL42 (a virulent b serotype strain) as a lipoprotein, most likely anchored in the outer leaflet of the cytoplasmic membrane.…”

“…However, model building has shown that it is possible to accomodate a heme molecule in these binding sites [72]. There is no structure of apoOppAHi.…”