| Literature DB >> 27379833 |
Nestor Concha1, Jianzhong Huang1, Xiaopeng Bai2, Andrew Benowitz1, Pat Brady1, LaShadric C Grady2, Luz Helena Kryn3, David Holmes1, Karen Ingraham1, Qi Jin1, Laura Pothier Kaushansky2, Lynn McCloskey1, Jeffrey A Messer2, Heather O'Keefe2, Amish Patel2, Alexander L Satz2, Robert H Sinnamon1, Jessica Schneck1, Steve R Skinner2, Jennifer Summerfield2, Amy Taylor1, J David Taylor1, Ghotas Evindar2, Robert A Stavenger1.
Abstract
Undecaprenyl pyrophosphate synthase (UppS) is an essential enzyme in bacterial cell wall synthesis. Here we report the discovery of Staphylococcus aureus UppS inhibitors from an Encoded Library Technology screen and demonstrate binding to the hydrophobic substrate site through cocrystallography studies. The use of bacterial strains with regulated uppS expression and inhibitor resistant mutant studies confirmed that the whole cell activity was the result of UppS inhibition, validating UppS as a druggable antibacterial target.Entities:
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Year: 2016 PMID： 27379833 DOI： 10.1021/acs.jmedchem.6b00746
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446