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https://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 |
DOI: | 10.2174/138945012803530170 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1022240 http://purl.org/au-research/grants/nhmrc/565526 |
Published version: | http://dx.doi.org/10.2174/138945012803530170 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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