2020
DOI: 10.1021/acsmedchemlett.9b00627
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Inhibition of Nonessential Bacterial Targets: Discovery of a Novel Serine O-Acetyltransferase Inhibitor

Abstract: In ϒ-proteobacteria and Actinomycetales, cysteine biosynthetic enzymes are indispensable during persistence and become dispensable during growth or acute infection. The biosynthetic machinery required to convert inorganic sulfur into cysteine is absent in mammals; therefore, it is a suitable drug target. We searched for inhibitors of Salmonella serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of l-cysteine biosynthesis. The virtual screening of three ChemDiv focused libraries co… Show more

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Cited by 23 publications
(18 citation statements)
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“…Since the primary structure of SAT is highly conserved among bacteria, [ 38 ] the virtual screening of our in-house library was performed using the available crystal structures of Ec SAT (pdb code: 1T3D) and Hi SAT (pdb code: 1SSM), setting the experimental parameters as previously reported by us [ 37 ]. After this preliminary analysis, a total of 7 compounds were identified and selected to be evaluated on the recombinant enzyme from S. typhimurium .…”
Section: Resultsmentioning
confidence: 99%
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“…Since the primary structure of SAT is highly conserved among bacteria, [ 38 ] the virtual screening of our in-house library was performed using the available crystal structures of Ec SAT (pdb code: 1T3D) and Hi SAT (pdb code: 1SSM), setting the experimental parameters as previously reported by us [ 37 ]. After this preliminary analysis, a total of 7 compounds were identified and selected to be evaluated on the recombinant enzyme from S. typhimurium .…”
Section: Resultsmentioning
confidence: 99%
“…After this preliminary analysis, a total of 7 compounds were identified and selected to be evaluated on the recombinant enzyme from S. typhimurium . The enzyme used in these assays has a K m ,Ser = 1.07 ± 0.15 mM, a K m,AcCoA = 0.17 ± 0.04 mM, k cat = 3813 ± 169 min −1 [ 37 ]. The assay conditions for the initial screening were set to improve the sensitivity of the assay towards both competitive and uncompetitive inhibitors, i.e., the concentration of both substrates was equal to K m .…”
Section: Resultsmentioning
confidence: 99%
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