Prokaryotic substrate-binding proteins as targets for antimicrobial therapies

Counago, Rafael M., McDevitt, Christopher A., Ween, Miranda P. and Kobe, Bostjan (2012) Prokaryotic substrate-binding proteins as targets for antimicrobial therapies. Current Drug Targets, 13 11: 1400-1410. doi:10.2174/138945012803530170

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Author Counago, Rafael M.
McDevitt, Christopher A.
Ween, Miranda P.
Kobe, Bostjan
Title Prokaryotic substrate-binding proteins as targets for antimicrobial therapies
Journal name Current Drug Targets   Check publisher's open access policy
ISSN 1389-4501
Publication date 2012-10-01
Sub-type Article (original research)
DOI 10.2174/138945012803530170
Volume 13
Issue 11
Start page 1400
End page 1410
Total pages 11
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Collection year 2013
Language eng
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.
Keyword ABC transporter
ATP-binding cassette
Bacterial pathogens
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
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Created: Thu, 04 Oct 2012, 11:16:49 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences