Artificial control of protein activity

Manuela Bersellini

Research output: ThesisThesis fully internal (DIV)

448 Downloads (Pure)

Abstract

Cells are confined environments that contain numerous different, densely packed molecules and where many biological processes occur simultaneously. Therefore, tight control of protein activity is necessary for the correct functioning of the cellular machinery and is essential for every living organism. The study and design of artificially regulated proteins improves our understanding of natural metabolic pathways and has important applications in synthetic biology and drug design and delivery. Furthermore, introducing artificial regulation into proteins or enzymes allowed the design switches whose activity is dependent on external stimuli and/or changes in the environment and can be valuable for the design of biosensors.
This thesis describes our work in the field of artificial control of protein activity. The first part of this thesis focuses on the design of artificial regulation strategies to modulate the activity of natural and artificial enzymes. First, two methodologies are presented to mediate the reassembly of two inactive fragments of a split enzyme for small molecules and metal ions recognition, respectively. A strategy to activate an artificial metalloenzyme by coordination of metal ions is also presented. In the second part of this thesis a distinct aspect of controlling protein function is explored that consists on the introduction of catalytic potential in proteins that do not show any native activity. In this context, three proteins belonging to the family of multidrug resistance regulators were studied for their use as scaffolds in the design of artificial metalloenzymes for Cu(II)-catalyzed asymmetric reactions.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Roelfes, Johannes, Supervisor
  • Browne, Wesley, Assessment committee
  • Merkx, M., Assessment committee, External person
  • Otto, Sijbren, Assessment committee
Award date3-Nov-2017
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-034-0134-8
Electronic ISBNs978-94-034-0133-1
Publication statusPublished - 2017

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