4K19

The structure of Human Siderocalin bound to the bacterial siderophore fluvibactin

Summary for 4K19

• Entry DOI: 10.2210/pdb4k19/pdb
• Descriptor: Neutrophil gelatinase-associated lipocalin, FE (III) ION, GLYCEROL, ... (8 entities in total)
• Functional Keywords: beta barrel, antibacterial, siderophore, metal binding protein-inhibitor complex, metal binding protein/inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : P80188
• Total number of polymer chains: 3
• Total formula weight: 64722.39

Authors

Correnti, C.,Clifton, M.C.,Strong, R.K. (deposition date: 2013-04-04, release date: 2013-07-31, Last modification date: 2024-11-06)

Primary citation

Allred, B.E.,Correnti, C.,Clifton, M.C.,Strong, R.K.,Raymond, K.N.
Siderocalin Outwits the Coordination Chemistry of Vibriobactin, a Siderophore of Vibrio cholerae.
Acs Chem.Biol., 8:1882-1887, 2013

PubMed 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.

PubMed: 23755875
DOI: 10.1021/cb4002552

Experimental method

X-RAY DIFFRACTION (2.74 Å)