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), transbilayer movement, periplasmic space.
Current Drug Targets
Title:Prokaryotic Substrate-Binding Proteins as Targets for Antimicrobial Therapies
Volume: 13 Issue: 11
Author(s): Rafael M. Counago, Christopher A. McDevitt, Miranda P. Ween and Bostjan Kobe
Affiliation:
Keywords: ABC transporter, ATP-binding cassette, antimicrobials, bacterial pathogens, Cluster A-1 SBP, drug design, metal binding, substrate-binding protein (SBP), transbilayer movement, periplasmic space.
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.
Export Options
About this article
Cite this article as:
M. Counago Rafael, A. McDevitt Christopher, P. Ween Miranda and Kobe Bostjan, Prokaryotic Substrate-Binding Proteins as Targets for Antimicrobial Therapies, Current Drug Targets 2012; 13 (11) . https://dx.doi.org/10.2174/138945012803530170
DOI https://dx.doi.org/10.2174/138945012803530170 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
Therapeutic Chemical and RNA Design with Artificial Intelligence
Computer-Aided Drug Design (CADD) has emerged as a fundamental component of modern drug discovery. Molecular docking facilitates virtual screening on a large scale through structural simulations. However, traditional CADD approaches face significant limitations, as they can only screen known compounds from existing libraries. PubChem, as the most widely used chemical ...read more

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
A Brief Overview of Antimicrobial Peptides Containing Unnatural Amino Acids and Ligand-Based Approaches for Peptide Ligands
Current Topics in Medicinal Chemistry Systemic Inflammatory Response as a Risk and Prognosis Factor in Ventilator-Associated Pneumonia
Current Respiratory Medicine Reviews Stem Cells and Congenital Heart Disease: The Future Potential Clinical Therapy Beyond Current Treatment
Current Cardiology Reviews Bacterial Adaptation and Infection
Inflammation & Allergy - Drug Targets (Discontinued) Synthesis, Structure and Antibacterial Evaluation of Some N-substituted 3-amino-5-hydroxy-4-phenyl-1H-pyrazole-1-carboxamides
Medicinal Chemistry Scintigraphic Imaging of Inflammatory Processes
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Antimicrobial Peptides and Peptidomimetics - Potent Therapeutic Allies for Staphylococcal Infections
Current Pharmaceutical Design Citrobacter braakii Bacteremia: Case Report and Review of the Literature
Infectious Disorders - Drug Targets Pseudomonas aeruginosa Invades Human Aortic Endothelial Cells and Induces Cell Damage in vitro
Cardiovascular & Hematological Disorders-Drug Targets Heart Failure in Acute Ischemic Stroke
Current Cardiology Reviews Hallmarks in the Therapeutic Approach of Aortic Aneurysms: The Main Contributors
Current Pharmaceutical Design Medicinal Herbs with Anti-Inflammatory Activities for Natural and Organic Healing
Current Organic Chemistry Q Fever and Coxiella burnetii: Immune Response and Pathogenesis
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Antibacterial Efficacy of Abrus precatorius L. and Asystasia gangetica (L.) T. Anderson
Anti-Infective Agents Anionic Antimicrobial Peptides from Eukaryotic Organisms and their Mechanisms of Action
Current Chemical Biology Biofilms and their Role in the Resistance of Pathogenic Candida to Antifungal Agents
Current Drug Targets Pulmonary Disease in Beta-Thalassemia
Current Respiratory Medicine Reviews Importance of Oral Health in Pregnancy: A Mini-symposium
Current Women`s Health Reviews Macrophage Heterogeneity: Relevance and Functional Implications in Atherosclerosis
Current Vascular Pharmacology <i>E. hirae</i> Causing Biliary Tract Infection in a Patient with Cholangiocarcinoma: A Case Report
Infectious Disorders - Drug Targets