Optimization of CarG crystals

Carbapenems are one of the most widely used groups of antibiotics because of their broad spectrum against both gram positive and gram negative bacteria. The biosynthesis of the simplest carbapenem, 1-carbapen-2-em-3- carboxylic acid (Car) is controlled by an operon of eight genes, CarA-H. CarG i...

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Autor principal: Persson, Teres
Formato: First cycle, G2E
Lenguaje:sueco
Inglés
Publicado: 2012
Materias:
Acceso en línea:https://stud.epsilon.slu.se/4331/
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author Persson, Teres
author_browse Persson, Teres
author_facet Persson, Teres
author_sort Persson, Teres
collection Epsilon Archive for Student Projects
description Carbapenems are one of the most widely used groups of antibiotics because of their broad spectrum against both gram positive and gram negative bacteria. The biosynthesis of the simplest carbapenem, 1-carbapen-2-em-3- carboxylic acid (Car) is controlled by an operon of eight genes, CarA-H. CarG is believed to possess a function of self-resistance but the mechanism is not solved. The structure of CarG was solved a few years ago. The aim of this study was to improve the crystal quality to open up for further binding studies on CarG. The protein was purified in a 4 step process; Ni2+-column, desalting, MonoQ and gelfiltration. MonoQ was added to the previous protocol with hope to further purify the protein. Different screening protocols were used and as in earlier studies of CarG, AmSO4 was a suitable precipitant. Crystals were obtained in a concentration range between 1.3-1.8 M AmSO4 and pH 7.5 and 8, respectively. Using these conditions seeding techniques and cocrystallization with imipenem and meropenem were performed. In this study I show that by adding MonoQ chromatography to the purification protocol bigger crystals and more single crystals can be obtained. Seeding, in drops with no substrate added, resulted in more square-shaped crystals but often much thinner crystals. Results from cocrystallization and seeding with imipenem show no improvement in crystal quality. Cocrystallization with meropenem gave clear crystals but was not further improved by seeding.
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spelling RepoSLU43312012-06-28T12:37:11Z https://stud.epsilon.slu.se/4331/ Optimization of CarG crystals Persson, Teres Chemistry Carbapenems are one of the most widely used groups of antibiotics because of their broad spectrum against both gram positive and gram negative bacteria. The biosynthesis of the simplest carbapenem, 1-carbapen-2-em-3- carboxylic acid (Car) is controlled by an operon of eight genes, CarA-H. CarG is believed to possess a function of self-resistance but the mechanism is not solved. The structure of CarG was solved a few years ago. The aim of this study was to improve the crystal quality to open up for further binding studies on CarG. The protein was purified in a 4 step process; Ni2+-column, desalting, MonoQ and gelfiltration. MonoQ was added to the previous protocol with hope to further purify the protein. Different screening protocols were used and as in earlier studies of CarG, AmSO4 was a suitable precipitant. Crystals were obtained in a concentration range between 1.3-1.8 M AmSO4 and pH 7.5 and 8, respectively. Using these conditions seeding techniques and cocrystallization with imipenem and meropenem were performed. In this study I show that by adding MonoQ chromatography to the purification protocol bigger crystals and more single crystals can be obtained. Seeding, in drops with no substrate added, resulted in more square-shaped crystals but often much thinner crystals. Results from cocrystallization and seeding with imipenem show no improvement in crystal quality. Cocrystallization with meropenem gave clear crystals but was not further improved by seeding. 2012-06-20 First cycle, G2E NonPeerReviewed application/pdf sv https://stud.epsilon.slu.se/4331/7/persson_t_120620.pdf Persson, Teres, 2012. Optimization of CarG crystals : a protein involved in the biosynthesis of 1-carbapen-2-em-3-carboxylic acid (Car); a beta-lactam antibiotic. First cycle, G2E. Uppsala: (NL, NJ) > Dept. of Molecular Biology (until 131231) <https://stud.epsilon.slu.se/view/divisions/4025.html> urn:nbn:se:slu:epsilon-s-1285 eng
spellingShingle Chemistry
Persson, Teres
Optimization of CarG crystals
title Optimization of CarG crystals
title_full Optimization of CarG crystals
title_fullStr Optimization of CarG crystals
title_full_unstemmed Optimization of CarG crystals
title_short Optimization of CarG crystals
title_sort optimization of carg crystals
topic Chemistry
url https://stud.epsilon.slu.se/4331/
https://stud.epsilon.slu.se/4331/