NMR Structure‐Based Optimization of Staphylococcus aureus Sortase A Pyridazinone Inhibitors
نویسندگان
چکیده
منابع مشابه
Discovery of Staphylococcus aureus sortase A inhibitors using virtual screening and the relaxed complex scheme.
Staphylococcus aureus is the leading cause of hospital-acquired infections in the United States. The emergence of multidrug-resistant strains of S. aureus has created an urgent need for new antibiotics. Staphylococcus aureus uses the sortase A enzyme to display surface virulence factors suggesting that compounds that inhibit its activity will function as potent anti-infective agents. Here, we r...
متن کاملModelling Staphylococcus aureus-induced septicemia using NMR.
We present a novel NMR-based study of the molecular aspects of the "attack" on human red blood cells (RBCs) by growing bacteria. Staphylococcus aureus expresses virulence factors, including alpha-hemolysin, which contribute to the clinical condition known as septic shock. alpha-Hemolysin is a pore-forming toxin and its secretion increases the permeability of a range of mammalian cell types infe...
متن کاملStaphylococcus aureus Sortase A-Mediated Incorporation of Peptides: Effect of Peptide Modification on Incorporation
The endogenous Staphylococcus aureus sortase A (SrtA) transpeptidase covalently anchors cell wall-anchored (CWA) proteins equipped with a specific recognition motif (LPXTG) into the peptidoglycan layer of the staphylococcal cell wall. Previous in situ experiments have shown that SrtA is also able to incorporate exogenous, fluorescently labelled, synthetic substrates equipped with the LPXTG moti...
متن کاملLocalization and mutagenesis of the sorting signal binding site on sortase A from Staphylococcus aureus.
Surface proteins in Gram-positive bacteria are anchored to the cell wall by the action of sortase enzymes. The Staphylococcus aureus sortase A (SrtA) protein anchors proteins by recognizing a cell wall sorting signal containing the amino acid sequence LPXTG. To understand how SrtA binds this sequence, we carried out NMR studies of new peptidyl-cyanoalkene and peptidyl-sulfhydryl inhibitors that...
متن کاملMolecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A.
The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded as promising candidates for countermeasures against bacteri...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: The FASEB Journal
سال: 2018
ISSN: 0892-6638,1530-6860
DOI: 10.1096/fasebj.2018.32.1_supplement.797.10