Computational investigation of acyl-CoA thioesterase I (TesA) from the bacteria Pseudomonas aeruginosa in complexes with ibuprofen and naproxen derivatives

Ilić, Krunoslav (2015) Computational investigation of acyl-CoA thioesterase I (TesA) from the bacteria Pseudomonas aeruginosa in complexes with ibuprofen and naproxen derivatives. Diploma thesis, Faculty of Science > Department of Biology.

[img]
Preview
PDF
Language: Croatian

Download (3MB) | Preview

Abstract

GDSL hydrolases are relatively poorly described enzyme family. They contain a GDSL structural motif centered around nucleophilic serine from catalytic triad. They are characterized by substrate promiscuity, which makes them an interesting area of research, both for fundamental scientific value and potential uses in pharmaceutic and biotech industry. One of the enzymes from that family shown to be an interesting research target is Acyl-CoA thioesterase (TesA) from Pseudomonas aeruginosa, which was studied in this thesis. Computational biochemistry methods, primarily Monte Carlo conformational search and molecular dynamics simulations, were used to test possibilities of catalytically productive substrate binding for ibuprofen and naproxen derivatives. Key interactions for active site binding were identified, as well as differences in binding between enantiomers of the same compound. Amino acid mutation L78F was introduced in silico and its effect on substrate binding and enantioselectivity was computationally assessed. Productive binding was obtained for R-ibuprofen derivate, both with wild-type enzyme and L78F mutant, as well as for R-naproxen derivate with mutated enzyme. Hydrophobic cavity for substrate binding was found in vicinity of the enzyme active site and non-bonding interactions required for catalysis were described, as well as the effect of L78F mutation on those interactions.

Item Type: Thesis (Diploma thesis)
Keywords: GDSL hydrolases, enantioselectivity, molecular dynamics, Monte Carlo conformational search
Supervisor: Bertoša, Branimir
Date: 2015
Number of Pages: 35
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 04 Mar 2016 13:10
Last Modified: 04 Mar 2016 13:10
URI: http://digre.pmf.unizg.hr/id/eprint/4541

Actions (login required)

View Item View Item

Nema podataka za dohvacanje citata