A5024902459- Enzyme Structure and Function
- Microbial Natural Products and Biosynthesis
- Signaling Pathways in Disease
- Peptidase Inhibition and Analysis
- Fungal Infections and Studies
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
UCB Pharma (United States)
2021-2023
Center for Infectious Disease Research
2021-2023
Abstract The design of proteins that bind to a specific site on the surface target protein using no information other than three-dimensional structure remains challenge 1–5 . Here we describe general solution this problem starts with broad exploration vast space possible binding modes selected region surface, and then intensifies search in vicinity most promising modes. We demonstrate applicability approach through de novo 12 diverse targets different shapes properties. Biophysical...
Due to rising rates of antifungal drug resistance and a limited armamentarium treatments, there is paramount need for novel drugs treat systemic fungal infections. Calcineurin has been established as an essential conserved virulence factor in several fungi, making it attractive target.
Acetyl CoA synthetases (ACSs) are
The compound ethyl-adenosyl monophosphate ester (ethyl-AMP) has been shown to effectively inhibit acetyl-CoA synthetase (ACS) enzymes and facilitate the crystallization of fungal ACS in various contexts. In this study, addition ethyl-AMP a bacterial from Legionella pneumophila resulted determination co-crystal structure previously elusive structural genomics target. dual functionality both inhibiting promoting establishes its significance as valuable resource for advancing investigations...
Abstract Calcineurin is an essential virulence factor that conserved across human fungal pathogens including Cryptococcus neoformans , Aspergillus fumigatus and Candida albicans . Although excellent target for antifungal drug development, the serine-threonine phosphatase activity of calcineurin in mammals inhibition this results immunosuppression. FK506 (tacrolimus) a naturally produced macrocyclic compound inhibits by binding to immunophilin FKBP12. Previously, our calcineurin-FK506-FKBP12...