Dissertation/ Thesis
Oligomeric structures of metabolic protein assemblies - Structure-function analysis of acetyl-CoA carboxylase and urease
| Title: | Oligomeric structures of metabolic protein assemblies - Structure-function analysis of acetyl-CoA carboxylase and urease |
|---|---|
| Authors: | Anton, Leonie |
| Contributors: | Maier, Timm, Basler, Marek |
| Publication Year: | 2020 |
| Collection: | University of Basel: edoc |
| Description: | Oligomeric protein assemblies play a pivotal role in metabolism. The advantages of such complexes are increased stability, protection from degradation and additional options for regulation through allostery. The two enzymes discussed in this thesis utilize oligomerization as a central mechanism, to shield from damaging conditions and control their activity. Urease is a nickel-metalloenzyme with varying assembly structures expressed in all branches of life except animals and is an essential part of the nitrogen cycle. It catalyzes the breakdown of urea into ammonia, which is used as a nitrogen source. Oligomerization of urease leads to the local increase of ammonia in a concentrated area and contributes to urease stability in extreme environments. Ureases have a huge impact on agricultural practices, but their function as virulence factors in pathogens also makes them important drug targets. Acetyl-CoA Carboxylase (ACC) catalyzes the first and rate limiting step in the production of fatty acids. Acetyl-CoA is carboxylated by ACC in two consecutive and distinct reactions, forming malonyl-CoA. Fatty acid synthase (FAS) uses malonyl-CoA as a precursor for the formation of fatty acids. Eukaryotic ACCs are multienzymes, which contain all the catalytic domains in a single polypeptide chain. Human ACC is a dimer and oligomerizes into a filament in its most active state. Upregulation of ACC activity has been linked to cancer, metabolic syndrome and viral infections. The aim of this thesis is the investigation of the mechanisms leading to oligomerization of these essential enzymes by using cryo-electron microscopy (cryo-EM). In chapter two, the nickel –metalloenzyme urease of Yersinia enterocolitica is revealed to form a tetramer-of-trimers. A similar assembly has only been observed for the pathogen Helicobacter pylori, where it is described as a crucial factor in survival of acidic environments. Including higher order aberration correction in data processing of cryoEM movies, a reconstruction of Y. enterocolitica urease ... |
| Document Type: | thesis |
| File Description: | application/pdf |
| Language: | English |
| Relation: | https://edoc.unibas.ch/79024/1/LeonieAnton_Dissertation_edoc.pdf; Anton, Leonie. Oligomeric structures of metabolic protein assemblies - Structure-function analysis of acetyl-CoA carboxylase and urease. 2020, Doctoral Thesis, University of Basel, Faculty of Science.; urn:urn:nbn:ch:bel-bau-diss137721 |
| Availability: | https://edoc.unibas.ch/79024/ https://edoc.unibas.ch/79024/1/LeonieAnton_Dissertation_edoc.pdf |
| Rights: | cc_by_nc ; info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.EE22C02B |
| Database: | BASE |
| Description not available. |