ArticleAntimicrobial agents and chemotherapy2014
A structural biology approach enables the development of antimicrobials targeting bacterial immunophilins.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 22 citations in OpenAlex.
- High Affinity Inhibitors of the Macrophage Infectivity Potentiator Protein fromACS infectious diseases · 2024Article
- Inhibition of macrophage infectivity potentiator inFrontiers in cellular and infection microbiology · 2024Article
- Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis.PLoS pathogens · 2023Article
- Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major.The Journal of antimicrobial chemotherapy · 2022Article
- Uncharted territories in the discovery of antifungal and antivirulence natural products from bacteria.Computational and structural biotechnology journal · 2021Review
- Recent contributions of structure-based drug design to the development of antibacterial compounds.Current opinion in microbiology · 2015Review
- Structural Genomics Support for Infectious Disease Drug Design.ACS infectious diseases · 2015Article
- Novel Cycloheximide Derivatives Targeting the Moonlighting Protein Mip Exhibit Specific Antimicrobial Activity Against Legionella pneumophila.Frontiers in bioengineering and biotechnology · 2015Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
Macrophage infectivity potentiators (Mips) are immunophilin proteins and essential virulence factors for a range of pathogenic organisms. We applied a structural biology approach to characterize a Mip from Burkholderia pseudomallei (BpML1), the causative agent of melioidosis. Crystal structure and nuclear magnetic resonance analyses of BpML1 in complex with known macrocyclics and other derivatives led to the identification of a key chemical scaffold. This scaffold possesses inhibitory potency for BpML1 without the immunosuppressive components of related macrocyclic agents. Biophysical characterization of a compound series with this scaffold allowed binding site specificity in solution and potency determinations for rank ordering the set. The best compounds in this series possessed a low-micromolar affinity for BpML1, bound at the site of enzymatic activity, and inhibited a panel of homologous Mip proteins from other pathogenic bacteria, without demonstrating toxicity in human macrophages. Importantly, the in vitro activity of BpML1 was reduced by these compounds, leading to decreased macrophage infectivity and intracellular growth of Burkholderia pseudomallei. These compounds offer the potential for activity against a new class of antimicrobial targets and present the utility of a structure-based approach for novel antimicrobial drug discovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.