Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/74804
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Type: Journal article
Title: Prokaryotic substrate-binding proteins as targets for antimicrobial therapies
Author: Counago, R.
McDevitt, C.
Ween, M.
Kobe, B.
Citation: Current Drug Targets, 2012; 13(11):1400-1410
Publisher: Bentham Science Publishers Ltd.
Issue Date: 2012
ISSN: 1389-4501
1873-5592
Statement of
Responsibility: 
M. Counago, Rafael; A. McDevitt, Christopher; P. Ween, Miranda; Kobe, Bostjan
Abstract: The rapid emergence of multidrug-resistant bacteria over the last two decades has catalyzed a shift away from traditional antibiotic development strategies and encouraged the search for unconventional drug targets. Prokaryotic substrate- binding proteins (SBPs), together with their cognate ATP-binding cassette (ABC) transporters, facilitate the unidirectional, transbilayer movement of specific extracytosolic cargoes against a concentration gradient, powered by ATP hydrolysis. In Gram-negative bacteria, SBPs are found in the periplasmic space, whereas in Gram-positive organisms these proteins are anchored to the outer cell wall by a lipid moiety. SBPs are vital components of the substrate-translocation machinery, as they determine cargo specificity and are involved in coupling the cargo uptake process with ABC transporter- mediated ATP hydrolysis. In this review, we focus on "Cluster A-1" divalent metal-binding proteins from within the SBP family. Acquisition of transition row metal ions is essential for bacterial colonization and virulence and Cluster A-1 SBPs play an integral role in this process. Cluster A-1 SBPs lack homologs in humans, bypass the need to deliver compounds into the bacterial cell, and are therefore potential drug targets against Gram-positive bacteria. Here we discuss the role SBPs play in the prokaryotic substrate-translocation machinery with emphasis in the substrate-binding mechanism of Cluster A-1 SBPs, the role of these proteins in virulence and their potential use as drug targets.
Keywords: ABC transporter; ATP-binding cassette; antimicrobials; bacterial pathogens; Cluster A-1 SBP; drug design; metal binding; substrate-binding protein (SBP).
Rights: © 2012 Bentham Science Publishers
RMID: 0020121961
DOI: 10.2174/138945012803530170
Grant ID: http://purl.org/au-research/grants/nhmrc/1022240
http://purl.org/au-research/grants/nhmrc/565526
Appears in Collections:Molecular and Biomedical Science publications

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