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Journal of Bacteriology, June 2004, p. 3903-3910, Vol. 186, No. 12
0021-9193/04/$08.00+0 DOI: 10.1128/JB.186.12.3903-3910.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Structural Basis for Iron Binding and Release by a Novel Class of Periplasmic Iron-Binding Proteins Found in Gram-Negative Pathogens
Stephen R. Shouldice,1 Robert J. Skene,2 Douglas R. Dougan,2 Gyorgy Snell,2 Duncan E. McRee,3 Anthony B. Schryvers,1* and Leslie W. Tari3*
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada T2N 4N1,1
Syrrx Inc.,2
ActiveSight, San Diego, California 921213
Received 8 January 2004/
Accepted 2 March 2004
We have determined the 1.35- and 1.45-Å structures, respectively, of closed and open iron-loaded forms of Mannheimia haemolytica ferric ion-binding protein A. M. haemolytica is the causative agent in the economically important and fatal disease of cattle termed shipping fever. The periplasmic iron-binding protein of this gram-negative bacterium, which has homologous counterparts in many other pathogenic species, performs a key role in iron acquisition from mammalian host serum iron transport proteins and is essential for the survival of the pathogen within the host. The ferric (Fe3+) ion in the closed structure is bound by a novel asymmetric constellation of four ligands, including a synergistic carbonate anion. The open structure is ligated by three tyrosyl residues and a dynamically disordered solvent-exposed anion. Our results clearly implicate the synergistic anion as the primary mediator of global protein conformation and provide detailed insights into the molecular mechanisms of iron binding and release in the periplasm.
* Corresponding author. Mailing address for Anthony B. Schryvers: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1. Phone: (858) 349-8770. Fax: (403) 270-2772. E-mail:
schryver{at}ucalgary.ca. Mailing address for Leslie W. Tari: ActiveSight Inc., 4045 Sorrento Valley Blvd., San Diego, CA 92121. Phone: (858) 349-8770. Fax: (858) 455-6932. E-mail:
ltari{at}active-sight.com.
Journal of Bacteriology, June 2004, p. 3903-3910, Vol. 186, No. 12
0021-9193/04/$08.00+0 DOI: 10.1128/JB.186.12.3903-3910.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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