YorkSpace has migrated to a new version of its software. Access our Help Resources to learn how to use the refreshed site. Contact diginit@yorku.ca if you have any questions about the migration.
 

Measuring the Dynamics and Kinetics of OXA-58, a Class D Abeta-Lactamase from Acinetobacter Baumannii

Simple item page
dc.contributor.advisorGolemi-Kotra, Dasantila
dc.creatorGill, Preet Kamal Singh
dc.creatorWilson, Derek J.
dc.date.accessioned2015-12-16T19:15:13Z
dc.date.available2015-12-16T19:15:13Z
dc.date.copyright2015-05-28
dc.date.issued2015-12-16
dc.date.updated2015-12-16T19:15:13Z
dc.degree.disciplineChemistry
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractOXA-58 is a β-lactamase enzyme that bacteria Acinetobacter baumannii employ as their chief defense mechanism against β-lactam antibiotic treatment. The catalytic activity of OXA-58 and its mutants was monitored as they turned over a series of β-lactam antibiotics. Isothermal titration calorimetry (ITC) showed that the mutation of phenylalanine114 to isoleucine (F114I) had the most detrimental impact on the catalytic efficiency of the enzyme. Isoleucine has a more branched side chain than phenylalanine, which lead to decreased substrate binding and a low catalytic efficiency of F114I mutant. A custom made microfluidic chip coupled to Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) technique was used to study the dynamics of free enzyme and during its reactions with good substrate oxacillin and poor substrate imipenem. The conformational space that OXA-58 explores was constrained in the presence of substrate, suggestive of an induced fit model for catalysis-linked dynamics.
dc.identifier.urihttp://hdl.handle.net/10315/30642
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectChemistry
dc.subjectBiochemistry
dc.subjectBiology
dc.subject.keywordskinetics
dc.subject.keywordsdynamics
dc.subject.keywordsHDX
dc.subject.keywordsMS
dc.subject.keywordsHDX-MS
dc.subject.keywordsOXA-58
dc.subject.keywordsprotein
dc.subject.keywordscatalysis-linked dynamics
dc.subject.keywordsITC
dc.subject.keywordsisothermal titration calorimetry
dc.subject.keywordsmass spectrometry
dc.subject.keywordsmicrofluidics
dc.subject.keywordsAcinetobacter baumannii
dc.subject.keywordsβ-lactamase
dc.subject.keywordsβ-lactam
dc.titleMeasuring the Dynamics and Kinetics of OXA-58, a Class D Abeta-Lactamase from Acinetobacter Baumannii
dc.typeElectronic Thesis or Dissertation

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Gill_Preet_Kamal_S_2015_Masters.pdf
Size:
1.83 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 2 of 2
No Thumbnail Available
Name:
license.txt
Size:
1.83 KB
Format:
Plain Text
Description:
Download
No Thumbnail Available
Name:
YorkU_ETDlicense.txt
Size:
3.38 KB
Format:
Plain Text
Description:
Download

Collections

Chemistry

All items in the YorkSpace institutional repository are protected by copyright, with all rights reserved except where explicitly noted.