title: Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A.
abstract: In-silico virtual screening of bacterial surface enzyme Staphylococcus aureus Sortase A against commercial compound libraries using FlexX software package has led to the identification of novel inhibitors. Inhibition of enzyme catalytic activity was determined by monitoring the steady state cleavage of a model peptide substrate. Preliminary structure activity relationship studies on the lead compound resulted in the identification of compounds with improved activity. The most active compound has an IC50 value of 58 microM against the enzyme.
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, 901 14th Street South, Birmingham, AL 35294, USA.
authors.forename: Bala Chandra
authors.initials: BC
authors.lastname: Chenna
authors.forename: Bidhan A
authors.initials: BA
authors.lastname: Shinkre
authors.forename: Jason R
authors.initials: JR
authors.lastname: King
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Lucius
authors.forename: Sthanam V L
authors.initials: SV
authors.lastname: Narayana
authors.forename: Sadanandan E
authors.initials: SE
authors.lastname: Velu
mesh_terms: D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D031541:Fluorescence Resonance Energy Transfer; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015853:Cysteine Proteinase Inhibitors; D005663:Furans; D009025:Morpholines; D013876:Thiophenes; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases