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Phage Display on the Anti-infective Target 1-Deoxy-d-xylulose-5-phosphate Synthase Leads to an Acceptor-Substrate Competitive Peptidic Inhibitor.
Marcozzi, Alessio Masini, Tiziana Zhu, Di Pesce, Diego Illarionov, Boris Fischer, Markus Herrmann, Andreas Hirsch, Anna Katharina Herta
Marcozzi, Alessio
Masini, Tiziana
Zhu, Di
Pesce, Diego
Illarionov, Boris
Fischer, Markus
Herrmann, Andreas
Hirsch, Anna Katharina Herta
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2018-01-04
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Abstract
Enzymes of the 2-C-methyl-d-erythritol-4-phosphate pathway for the biosynthesis of isoprenoid precursors are validated drug targets. By performing phage display on 1-deoxy-d-xylulose-5-phosphate synthase (DXS), which catalyzes the first step of this pathway, we discovered several peptide hits and recognized false-positive hits. The enriched peptide binder P12 emerged as a substrate (d-glyceraldehyde-3-phosphate)-competitive inhibitor of Deinococcus radiodurans DXS. The results indicate possible overlap of the cofactor- and acceptor-substrate-binding pockets and provide inspiration for the design of inhibitors of DXS with a unique and novel mechanism of inhibition.
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Phage Display on the Anti-infective Target 1-Deoxy-d-xylulose-5-phosphate Synthase Leads to an Acceptor-Substrate Competitive Peptidic Inhibitor. 2018, 19 (1):58-65 Chembiochem
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en
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1439-7633