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Structure of Haemophilus influenzae Fe+3-binding protein reveals convergent evolution within a superfamily

Nature Structural Biology volume 4, pages 919–924 (1997)Cite this article

Abstract

The first crystal structure of the iron-transporter ferric ion-binding protein from Haemophilus influenzae (hFBP), at 1.6 Å resolution, reveals the structural basis for iron uptake and transport required by several important bacterial pathogens. Paradoxically, although hFBP belongs to a protein superfamily which includes human transferrin, iron binding in hFBP and transferrin appears to have developed independently by convergent evolution. Structural comparison of hFBP with other prokaryotic periplasmic transport proteins and the eukaryotic transferrins suggests that these proteins are related by divergent evolution from an anion-binding common ancestor, not from an iron-binding ancestor. The iron binding site of hFBP incorporates a water and an exogenous phosphate ion as iron ligands and exhibits nearly ideal octahedral metal coordination. FBP is highly conserved, required for virulence, and is a nodal point for free iron uptake in several Gram-negative pathogenic bacteria, thus providing a potential target for broad-spectrum antibacterial drug design against human pathogens such as H. influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis.

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Author notes

  1. Michele A. McTigue

    Present address: Agouron Pharmaceuticals, 3565 General Atomics Ct., San Diego, California, 92121, USA

Authors and Affiliations

  1. Department of Molecular Biology MB8, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, California, 92037, USA

    Christopher M. Bruns, Andrew S. Arvai & Duncan E. McRee

  2. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA

    Andrew J. Nowalk, Kevin G. Vaughan & Timothy A. Mietzner

Authors
  1. Christopher M. Bruns
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  2. Andrew J. Nowalk
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  4. Michele A. McTigue
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  5. Kevin G. Vaughan
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  6. Timothy A. Mietzner
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  7. Duncan E. McRee
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Correspondence to Duncan E. McRee.

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Bruns, C., Nowalk, A., Arvai, A. et al. Structure of Haemophilus influenzae Fe+3-binding protein reveals convergent evolution within a superfamily. Nat Struct Mol Biol 4, 919–924 (1997). https://doi.org/10.1038/nsb1197-919

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