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Bacteria in an intense competition for iron: Key component of the Campylobacter jejuni iron uptake system scavenges enterobactin hydrolysis product

DOI: 10.1073/pnas.1520829113 DOI Help

Authors: Daniel Raines (University of York) , Olga Moroz (University of York) , Elena Blagova (University of York) , Johan Turkenburg (University of York) , Keith Wilson (University of York) , Anne Duhme- Klair (University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences

State: Published (Approved)
Published: May 2016
Diamond Proposal Number(s): 7864

Open Access Open Access

Abstract: To acquire essential Fe(III), bacteria produce and secrete siderophores with high affinity and selectivity for Fe(III) to mediate its uptake into the cell. Here, we show that the periplasmic binding protein CeuE of Campylobacter jejuni, which was previously thought to bind the Fe(III) complex of the hexadentate siderophore enterobactin (Kd ∼ 0.4 ± 0.1 µM), preferentially binds the Fe(III) complex of the tetradentate enterobactin hydrolysis product bis(2,3-dihydroxybenzoyl-L-Ser) (H5-bisDHBS) (Kd = 10.1 ± 3.8 nM). The protein selects Λ-configured [Fe(bisDHBS)]2− from a pool of diastereomeric Fe(III)-bisDHBS species that includes complexes with metal-to-ligand ratios of 1:1 and 2:3. Cocrystal structures show that, in addition to electrostatic interactions and hydrogen bonding, [Fe(bisDHBS)]2− binds through coordination of His227 and Tyr288 to the iron center. Similar binding is observed for the Fe(III) complex of the bidentate hydrolysis product 2,3-dihydroxybenzoyl-L-Ser, [Fe(monoDHBS)2]3−. The mutation of His227 and Tyr288 to noncoordinating residues (H227L/Y288F) resulted in a substantial loss of affinity for [Fe(bisDHBS)]2− (Kd ∼ 0.5 ± 0.2 µM). These results suggest a previously unidentified role for CeuE within the Fe(III) uptake system of C. jejuni, provide a molecular-level understanding of the underlying binding pocket adaptations, and rationalize reports on the use of enterobactin hydrolysis products by C. jejuni, Vibrio cholerae, and other bacteria with homologous periplasmic binding proteins.

Journal Keywords: siderophore; Fe(III) uptake; periplasmic binding protein; enterobactin; Campylobacter jejuni

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 21/05/2016 17:58

Documents:
pnas.1520829113.pdf

Discipline Tags:

Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)