Phage Display on the Anti-infective Target 1-Deoxy-d-xylulose-5-phosphate Synthase Leads to an Acceptor-Substrate Competitive Peptidic Inhibitor.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621235
Title:
Phage Display on the Anti-infective Target 1-Deoxy-d-xylulose-5-phosphate Synthase Leads to an Acceptor-Substrate Competitive Peptidic Inhibitor.
Authors:
Marcozzi, Alessio; Masini, Tiziana; Zhu, Di; Pesce, Diego; Illarionov, Boris; Fischer, Markus; Herrmann, Andreas; Hirsch, Anna Katharina Herta ( 0000-0001-8734-4663 )
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.
Affiliation:
HIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
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
Journal:
Chembiochem : a European journal of chemical biology
Issue Date:
4-Jan-2018
URI:
http://hdl.handle.net/10033/621235
DOI:
10.1002/cbic.201700402
PubMed ID:
29119720
Type:
Article
Language:
en
ISSN:
1439-7633
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorMarcozzi, Alessioen
dc.contributor.authorMasini, Tizianaen
dc.contributor.authorZhu, Dien
dc.contributor.authorPesce, Diegoen
dc.contributor.authorIllarionov, Borisen
dc.contributor.authorFischer, Markusen
dc.contributor.authorHerrmann, Andreasen
dc.contributor.authorHirsch, Anna Katharina Hertaen
dc.date.accessioned2018-01-17T11:44:13Z-
dc.date.available2018-01-17T11:44:13Z-
dc.date.issued2018-01-04-
dc.identifier.citationPhage 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 Chembiochemen
dc.identifier.issn1439-7633-
dc.identifier.pmid29119720-
dc.identifier.doi10.1002/cbic.201700402-
dc.identifier.urihttp://hdl.handle.net/10033/621235-
dc.description.abstractEnzymes 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titlePhage Display on the Anti-infective Target 1-Deoxy-d-xylulose-5-phosphate Synthase Leads to an Acceptor-Substrate Competitive Peptidic Inhibitor.en
dc.typeArticleen
dc.contributor.departmentHIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalChembiochem : a European journal of chemical biologyen
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