Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A.
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.
Chenna
Bala Chandra
BC
Department of Chemistry, University of Alabama at Birmingham, 901 14th Street South, Birmingham, AL 35294, USA.
Shinkre
Bidhan A
BA
King
Jason R
JR
Lucius
Aaron L
AL
Narayana
Sthanam V L
SV
Velu
Sadanandan E
SE
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
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