ArticleThe Journal of biological chemistry2011
Structures of Cryptococcus neoformans protein farnesyltransferase reveal strategies for developing inhibitors that target fungal pathogens.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 62 citations in OpenAlex.
- Article
- Computational Approaches for Discovering Virulence Factors inJournal of fungi (Basel, Switzerland) · 2025Review
- Library Screening, In Vivo Confirmation, and Structural and Bioinformatic Analysis of Pentapeptide Sequences as Substrates for Protein Farnesyltransferase.International journal of molecular sciences · 2024Article
- Old and new strategies in therapy and diagnosis against fungal infections.Applied microbiology and biotechnology · 2024Review
- Phosphate availability conditions caspofungin tolerance, capsule attachment and titan cell formation inFrontiers in fungal biology · 2024Article
- Application of anti-fungal vaccines as a tool against emerging anti-fungal resistance.Frontiers in fungal biology · 2023Review
- Structure-Guided Discovery of Potent Antifungals that Prevent Ras Signaling by Inhibiting Protein Farnesyltransferase.Journal of medicinal chemistry · 2022Article
- Synthesis, Structural Characterization, and In Vitro and In Silico Antifungal Evaluation of Azo-Azomethine Pyrazoles (PhNMolecules (Basel, Switzerland) · 2021Article
- Antifungal Drug Resistance: Molecular Mechanisms inChemical reviews · 2021Review
- Structure-guided approaches to targeting stress responses in human fungal pathogens.The Journal of biological chemistry · 2020Review
- Novel Antifungal Agents and Their Activity againstJournal of fungi (Basel, Switzerland) · 2020Review
- Differential requirements of protein geranylgeranylation for the virulence of human pathogenic fungi.Virulence · 2019Article
- The farnesyltransferase β-subunit RAM1 regulates localization of RAS proteins and appressorium-mediated infection in Magnaporthe oryzae.Molecular plant pathology · 2019Article
- Roles for Stress Response and Cell Wall Biosynthesis Pathways in Caspofungin Tolerance inGenetics · 2019Article
- Isoprenoids and protein prenylation: implications in the pathogenesis and therapeutic intervention of Alzheimer's disease.Critical reviews in biochemistry and molecular biology · 2018Review
- Efficient farnesylation of an extended C-terminal C(The Journal of biological chemistry · 2018Article
- Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies.Chemical reviews · 2018Article
- The Aspergillus fumigatus farnesyltransferase β-subunit, RamA, mediates growth, virulence, and antifungal susceptibility.Virulence · 2017Article
- Targeting protein localization for anti-infective therapy.Virulence · 2017Article
- The antifungal pipeline: a reality check.Nature reviews. Drug discovery · 2017Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, including AIDS patients and transplant recipients. Few antifungals can treat C. neoformans infections, and drug resistance is increasing. Protein farnesyltransferase (FTase) catalyzes post-translational lipidation of key signal transduction proteins and is essential in C. neoformans. We present a multidisciplinary study validating C. neoformans FTase (CnFTase) as a drug target, showing that several anticancer FTase inhibitors with disparate scaffolds can inhibit C. neoformans and suggesting structure-based strategies for further optimization of these leads. Structural studies are an essential element for species-specific inhibitor development strategies by revealing similarities and differences between pathogen and host orthologs that can be exploited. We, therefore, present eight crystal structures of CnFTase that define the enzymatic reaction cycle, basis of ligand selection, and structurally divergent regions of the active site. Crystal structures of clinically important anticancer FTase inhibitors in complex with CnFTase reveal opportunities for optimization of selectivity for the fungal enzyme by modifying functional groups that interact with structurally diverse regions. A substrate-induced conformational change in CnFTase is observed as part of the reaction cycle, a feature that is mechanistically distinct from human FTase. Our combined structural and functional studies provide a framework for developing FTase inhibitors to treat invasive fungal infections.
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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.