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Identifier

000406866

Title

Structure-based virtual screening of potential inhibitors for peptidoglycan deacetylase BC1974 from Bacillus cereus

Alternative Title

In Silico επιλογή και μελέτη αναστολέων της απακετυλάσης πεπτιδογλυκάνης BC1974 από Bacillus cereus.

Author

Γκιουλμπασάνη, Μαριάνθη Α.

Thesis advisor

Ηλιόπουλος, Ηλίας
Μπουριώτης, Βασίλης

Abstract

Peptidoglycan is the essential cell wall of Bacillus cereus. Peptidoglycan GlcNAc deacetylases (PGNG-dacs) belong to the Carbohydrate Esterase Family 4 (CE4) and are necessary for bacterial evasion to lysozyme and immune responses. BC1974 is a PGNG-dac of B. cereus and exhibits 97% identity with BA1977, a bona fide peptidoglycan deacetylase involved in resistance to host lysozyme and required for full virulence from Bacillus anthracis, the etiological agent of anthrax. In order to identify potential inhibitors for BC1974, a structure-based virtual screening approach has been applied. We have searched in ZINC database for molecules that contain a hydroxamic moiety or the N-hydroxybenzamide as a substructure. Three compounds; 1-[(3,5-dimethyl-1,2-oxazol-4-yl)sulfonyl]-N-hydroxypiperidine-4-carboxamide (ZINC12560961), 1-(2,3-dihydro-1H-inden-5-ylsulfonyl)-N-hydroxypiperidine-4-carboxamide (ZINC12560959), 2-(1-adamantyl)-N-hydroxyacetamide (ZINC03866444), were selected for in vitro experiments. Fluorescent and radiometric assays were employed for the examination of the inhibitory effect of the selected compounds. Analysis of the results did not show any significant inhibition of BC1974 using two of the three compounds. The third one (ZINC03866444) showed an inhibitory effect but only using the radiolabeled glycol chitin substrate. A reason could be the affinity difference between the inhibitor and the substrates (GlcNAc5 and radiolabeled glycol chitin) for the binding site of BC1974. Furτher experiments need to be performed in order to clarify the inhibitory effect of the third inhibitor.

Language

English

Subject

B. Anthracis

B. Cereus

BA1977

Εικονική διαλογή βασισμένη στη δομή

Issue date

2017-03-17

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses

Type of Work--Post-graduate theses