title: Siderocalin outwits the coordination chemistry of vibriobactin, a siderophore of Vibrio cholerae.
abstract: The human protein siderocalin (Scn) inhibits bacterial iron acquisition by binding catechol siderophores. Several pathogenic bacteria respond by making stealth siderophores that are not recognized by Scn. Fluvibactin and vibriobactin, respectively of Vibrio fluvialis and Vibrio cholerae , include an oxazoline adjacent to a catechol. This chelating unit binds iron either in a catecholate or a phenolate-oxazoline coordination mode. The latter has been suggested to make vibriobactin a stealth siderophore without directly identifying the coordination mode in relation to Scn binding. We use Scn binding assays with the two siderophores and two oxazoline-substituted analogs and the crystal structure of Fe-fluvibactin:Scn to show that the oxazoline does not prevent Scn binding; hence, vibriobactin is not a stealth siderophore. We show that the phenolate-oxazoline coordination mode is present at physiological pH and is not bound by Scn. However, Scn binding shifts the coordination to the catecholate mode and thereby inactivates this siderophore.
authors.affiliation: Department of Chemistry, University of California , Berkeley, California 94720-1460, United States.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Allred
authors.forename: Colin
authors.initials: C
authors.lastname: Correnti
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Clifton
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Raymond
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002396:Catechols / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000071068:Lipocalin-2; D008958:Models, Molecular; D010080:Oxazoles / Q000737:chemistry / Q000378:metabolism*; D017262:Siderophores / Q000737:chemistry / Q000378:metabolism*; D014734:Vibrio cholerae / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D002396:Catechols; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D010080:Oxazoles; D017262:Siderophores; C040227:vibriobactin; D007501:Iron