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Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae

Müller, Axel, Severi, Emmanuele, Mulligan, Christopher, Watts, Andrew G, Kelly, David J, Wilson, Keith S, Wilkinson, Anthony J, Thomas, Gavin H (2006) Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae. The Journal of biological chemistry, 281 (331). pp. 22212-22222. ISSN 0021-9258. (doi:10.1074/jbc.M603463200) (KAR id:61635)

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Abstract

Extracytoplasmic solute receptors (ESRs) are important components of solute uptake systems in bacteria, having been studied extensively as parts of ATP binding cassette transporters. Herein we report the first crystal structure of an ESR protein from a functionally characterized electrochemical ion gradient dependent secondary transporter. This protein, SiaP, forms part of a tripartite ATP-independent periplasmic transporter specific for sialic acid in Haemophilus influenzae. Surprisingly, the structure reveals an overall topology similar to ATP binding cassette ESR proteins, which is not apparent from the sequence, demonstrating that primary and secondary transporters can share a common structural component. The structure of SiaP in the presence of the sialic acid analogue 2,3-didehydro-2-deoxy-N-acetylneuraminic acid reveals the ligand bound in a deep cavity with its carboxylate group forming a salt bridge with a highly conserved Arg residue. Sialic acid binding, which obeys simple bimolecular association kinetics as determined by stopped-flow fluorescence spectroscopy, is accompanied by domain closure about a hinge region and the kinking of an alpha-helix hinge component. The structure provides insight into the evolution, mechanism, and substrate specificity of ESR-dependent secondary transporters that are widespread in prokaryotes.

Item Type: Article
DOI/Identification number: 10.1074/jbc.M603463200
Subjects: Q Science
Q Science > QD Chemistry > QD431 Organic Chemistry- Biochemistry- Proteins, peptides, amino acids
Q Science > QD Chemistry > QD473 Physical properties in relation to structure
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Christopher Mulligan
Date Deposited: 10 May 2017 14:38 UTC
Last Modified: 06 Feb 2020 04:16 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61635 (The current URI for this page, for reference purposes)
Mulligan, Christopher: https://orcid.org/0000-0001-5157-4651
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