Lipases are enzymes that play fundamental roles in fat digestion and metabolism, and function at the interface formed between hydrophobic molecules and the surrounding aqueous environment. These interfacial interactions are thought to induce conformational changes in a "lid" region of the lipase, leading to a dramatic increase in activity. This thesis aims to provide insight into the interactions that govern lipase association with interfaces of di erent structural characteristics, and the possible conformational changes that arise as a function of these interactions. A multi-scale molecular simulation approach (combining atomistic and coarse-grained methods) was applied to study two different lipases with a range of interfaces, including "soft" biological surfaces and "hard" non-biological surfaces. Three major insights were gained from these studies. First, interactions of a small bacterial lipase (M37) with lipid interfaces resulted in substantial structural changes in a lid region, uncovering of the underlying active site. A mechanism of interfacial ac- tivation is proposed for this lipase. Second, the interaction of M37 with non-biological interfaces di er from lipid interfaces, leading to altered interfacial orientations with possible functional consequences. Third, the amino acid composition of the lid region of a yeast lipase (TLL) is shown to play crucial roles in lipase activation and structural stability.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:724950 |
| Date | January 2016 |
| Creators | Willems, Nathalie |
| Contributors | Sansom, Mark |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:7765c334-7c02-4190-a4b2-99ad315cfe52 |
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