Bukhari, Habib. Evolution and mechanism of fatty acid synthase multienzymes. 2015, PhD Thesis, University of Basel, Faculty of Science.
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Official URL: http://edoc.unibas.ch/diss/DissB_11542
In contrast structural and evolutionarily analysis revealed that animal FAS is related to polyketide synthase type I (PKS I), which is utilized by bacteria to synthesize a broad spectrum of secondary metabolites. Animal FAS is
an open X-shaped structure with catalytic domains not interrupted by the insertion of scaffolding elements but connected to each other via short not conserved linker sequences. Crystallographic data together with biochemical and electron microscopy (EM) analysis indicate that animal FAS displays an extraordinary degree of flexibility to ensure productive interactions between the active sites during the reaction cycle. Conformational changes most likely result from a combination of internal domain flexibility in the linker regions, which connects individual domains in the animal FAS. The second part of the thesis is thus dedicated to investigating how intra domain linking influences catalytic properties and conformational crosstalk between domains. This was achieved by generating more then 40 different constructs with various linker lenths. Combined structural and kinetic data from purified constructs helped us to better understand the emergent properties of the megasynthase system. A long-term goal is to use these insights for the construction of artificial multienzymes incorporating complete and complex molecular pathways.
|Advisors:||Maier, Timm and Lim, Roderick|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Maier)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||127 Seiten|
|Last Modified:||30 Jun 2016 10:59|
|Deposited On:||16 Feb 2016 14:38|
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