A5086445126- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Bacterial biofilms and quorum sensing
- Genomics and Phylogenetic Studies
- Microbial Natural Products and Biosynthesis
- Antimicrobial Resistance in Staphylococcus
- Biochemical and Structural Characterization
- Polyamine Metabolism and Applications
- Marine Sponges and Natural Products
- Peptidase Inhibition and Analysis
- Bioactive Compounds and Antitumor Agents
- DNA Repair Mechanisms
- Phytochemistry and biological activities of Ficus species
- Alkaloids: synthesis and pharmacology
- Machine Learning in Bioinformatics
- Bioinformatics and Genomic Networks
- Parasitic Infections and Diagnostics
- Cholesterol and Lipid Metabolism
- Mental Health Research Topics
- Biochemical and biochemical processes
- Lipid Membrane Structure and Behavior
- Toxin Mechanisms and Immunotoxins
- Cancer therapeutics and mechanisms
Sun Yat-sen University
2015-2024
As a class of essential enzymes in protein translation, aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) are organized into two classes 10 each, based on conserved active site architectures. The (αβ)2 glycyl-tRNA synthetase (GlyRS) many bacteria is an orphan aaRS whose sequence and unprecedented X-shaped structure distinct from those all other aaRSs, including bacterial eukaryotic GlyRSs. Here, we report cocrystal to elucidate how the GlyRS kingdom specifically recognizes its substrate...
To discover new agents active against methicillin-resistant Staphylococcus aureus (MRSA), in silico models derived from 5451 cell-based anti-MRSA assay data were developed using four machine learning methods, including naïve Bayesian, support vector (SVM), recursive partitioning (RP), and k-nearest neighbors (kNN). A total of 876 have been constructed based on physicochemical descriptors fingerprints. The overall predictive accuracies the best exceeded 80% for both training test sets. model...
Pseudellones A and B (1 2), a pair of irregularly bridged epimonothiodiketopiperazine diastereomers constructed from unusual 3-indolylglycine alanine residues, an alkaloid pseudellone C (3) possessing unique skeleton were isolated the marine-derived fungus Pseudallescheria ellipsoidea F42–3. Their structures determined by spectroscopic data, ECD calculation, X-ray single crystal diffraction. The biogenetic pathways 1–3 proposed, 1H-indole-3-carboxylic acid (4), plausible biosynthetic...
Abstract The polyketide natural product reveromycin A (RM-A) exhibits antifungal, anticancer, anti-bone metastasis, anti-periodontitis and anti-osteoporosis activities by selectively inhibiting eukaryotic cytoplasmic isoleucyl-tRNA synthetase (IleRS). Herein, a co-crystal structure suggests that the RM-A molecule occupies substrate tRNA Ile binding site of Saccharomyces cerevisiae IleRS ( Sc IleRS), partially mimicking . is facilitated copurified intermediate isoleucyl-adenylate (Ile-AMP)....
Indoleamine 2,3-dioxygenase (IDO), an immune checkpoint, is a promising target for cancer immunotherapy.
Abstract AaRSs (aminoacyl-tRNA synthetases) group into two ten-member classes throughout evolution, with unique active site architectures defining each class. Most are monomers or homodimers but, for no apparent reason, many bacterial GlyRSs heterotetramers consisting of catalytic α-subunits and tRNA-binding β-subunits. The heterotetrameric GlyRS from Escherichia coli (EcGlyRS) was historically tested whether its α- β-polypeptides, which encoded by a single mRNA gap three in-frame codons,...
Aminoacyl-tRNA synthetases (aaRSs) are promising antimicrobial targets due to their essential roles in protein translation, and expanding inhibitory mechanisms will provide new opportunities for drug discovery. We report here that halofuginone (HF), an herb-derived medicine, moderately inhibits prolyl-tRNA (ProRSs) from various pathogenic bacteria. A cocrystal structure of Staphylococcus aureus ProRS (SaProRS) with HF ATP analog was determined, which guided the design analogs. Compound 3...
Staphyloferrin B is a key siderophore secreted by Staphylococcus aureus to acquire ferric ions from host during infection, and its biosynthetic pathway has been validated develop efficient antibacterial agents. Herein, we report the crystal structure of AMP-bound SbnC S. (SaSbnC) as first representative type synthetases in biosynthesis α-hydroxycarboxylate siderophores. While specifically use α-ketoglutarate (α-KG) their carboxylic acid substrate, SaSbnC showed unique structural features...
Proteus vulgaris L-amino acid deaminase (pvLAAD) belongs to a class of bacterial membrane-bound LAADs mainly express in genus Proteus, Providencia and Morganella. These employ non-cleavable N-terminal twin-arginine translocation (Tat) peptide transport across membrane bind surface. Recent studies revealed that hydrophobic insertion sequence (INS) these also interacts with membrane. However, the functional significance INS-membrane interaction is not clear. In this study, we made...
Staphylopine (StP) and other nicotianamine-like metallophores are crucial for many pathogens to acquire the transition metals from hosts during invasion. CntL Staphylococcus aureus (SaCntL) catalyzes condensation of 2-aminobutyrate (Ab) moiety S-adenosylmethionine (SAM) with D-histidine in biosynthesis StP. Here, we report crystal structures SaCntL complex either SAM or two products. The structure consists an N-terminal four-helix bundle (holding catalytic residue E84) a C-terminal Rossmann...
Abstract Compounds (I)‐(III) exhibit no significant antibacterial activity.
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22942-2