title: The substrate-binding protein in bacterial ABC transporters: dissecting roles in the evolution of substrate specificity.
abstract: ATP-binding cassette (ABC) transporters, although being ubiquitous in biology, often feature a subunit that is limited primarily to bacteria and archaea. This subunit, the substrate-binding protein (SBP), is a key determinant of the substrate specificity and high affinity of ABC uptake systems in these organisms. Most prokaryotes have many SBP-dependent ABC transporters that recognize a broad range of ligands from metal ions to amino acids, sugars and peptides. Herein, we review the structure and function of a number of more unusual SBPs, including an ABC transporter involved in the transport of rare furanose forms of sugars and an SBP that has evolved to specifically recognize the bacterial cell wall-derived murein tripeptide (Mtp). Both these examples illustrate that subtle changes in binding-site architecture, including changes in side chains not directly involved in ligand co-ordination, can result in significant alteration of substrate range in novel and unpredictable ways.
authors.affiliation: Department of Biology, University of York, Wentworth Way, York Y010 5YW, U.K.
authors.forename: Abbas
authors.initials: A
authors.lastname: Maqbool
authors.affiliation: Department of Biology, University of York, Wentworth Way, York Y010 5YW, U.K.
authors.forename: Richard S P
authors.initials: RS
authors.lastname: Horler
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry, University of York, Wentworth Way, York Y010 5YW, U.K.
authors.forename: Axel
authors.initials: A
authors.lastname: Muller
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry, University of York, Wentworth Way, York Y010 5YW, U.K.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Wilkinson
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry, University of York, Wentworth Way, York Y010 5YW, U.K.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Wilson
authors.affiliation: Department of Biology, University of York, Wentworth Way, York Y010 5YW, U.K. gavin.thomas@york.ac.uk.
authors.forename: Gavin H
authors.initials: GH
authors.lastname: Thomas
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D005075:Biological Evolution; D008958:Models, Molecular; D009005:Monosaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D009005:Monosaccharides; D000255:Adenosine Triphosphate
keywords: adenosine 5′-triphosphate-binding cassette (ABC) transporter; evolution; substrate specificity; substrate-binding protein (SBP)