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

dc.contributor.author	Marcozzi, Alessio
dc.contributor.author	Masini, Tiziana
dc.contributor.author	Zhu, Di
dc.contributor.author	Pesce, Diego
dc.contributor.author	Illarionov, Boris
dc.contributor.author	Fischer, Markus
dc.contributor.author	Herrmann, Andreas
dc.contributor.author	Hirsch, Anna Katharina Herta
dc.date.accessioned	2018-01-17T11:44:13Z
dc.date.available	2018-01-17T11:44:13Z
dc.date.issued	2018-01-04
dc.identifier.citation	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	en
dc.identifier.issn	1439-7633
dc.identifier.pmid	29119720
dc.identifier.doi	10.1002/cbic.201700402
dc.identifier.uri	http://hdl.handle.net/10033/621235
dc.description.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.
dc.language.iso	en	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-sa/4.0/	*
dc.title	Phage Display on the Anti-infective Target 1-Deoxy-d-xylulose-5-phosphate Synthase Leads to an Acceptor-Substrate Competitive Peptidic Inhibitor.	en
dc.type	Article	en
dc.contributor.department	HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.	en
dc.identifier.journal	Chembiochem : a European journal of chemical biology	en
refterms.dateFOA	2018-06-12T18:08:03Z
html.description.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.