Öster, Carl (2017) Investigating interactions using solid state NMR: applications to biomolecular complexes. PhD thesis, University of Warwick.

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Abstract

Solid state NMR is a powerful method to obtain information on structure and dynamics of proteins, protein complexes, and other biomolecular assemblies, that due to solubility and size limitations cannot be achieved by other methods. This thesis is dedicated to the use of proton detected solid state NMR experiments at fast (60-100 kHz) magic angle spinning speeds to probe biomolecular structure, dynamics and intermolecular interactions. We used solvent paramagnetic relaxation enhancements to (i) speed up experiments and (ii) measure solvent accesibililty to map protein – protein interfaces. Further we use nuclear spin relaxation measurements to obtain information on protein dynamics in a small protein in two different ensembles; crystalline and precipitated in a > 300 kDa complex. We also apply a combined solution and solid state NMR approach to investigate the interactions between possibly the most promising antibiotic lead in modern time, teixobactin, and arguably the most exciting bacterial target, lipid II. Our most important results include a new method for probing protein-protein interactions using solvent paramagnetic relaxation enhancements, the first site specific dynamics measurements spanning a wide range of time scales obtained in a large protein complex using as little as 8 nanomoles of isotopically labelled material, the use of solvent paramagnetic relaxation enhancements to enable measurements of conformational exchange in a large protein complex and finally we have identified important conformational changes involved in the binding of teixobactin to cell wall precursor lipid II.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QD Chemistry
Library of Congress Subject Headings (LCSH):	Nuclear magnetic resonance spectroscopy, Chemistry, Biomolecules -- Analysis
Official Date:	August 2017
Dates:	Date Event August 2017 Submitted
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Lewandowski, Józef R.
Sponsors:	Marie Skłodowska Curie Initial Training Networks ( ITN)
Extent:	181 leaves) : illustrations, charts
Language:	eng

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