The Biochemistry Group
A major goal of protein engineering is the design of stabilized protein variants for use in many applications. In this project we use several strategies based on experience from our folding studies to stabilize the structure of our model protein carbonic anhydrase. Engineered proteins with varying stability and different surface structure are also employed to study the interaction with solid surfaces, a phenomenon that is very important in many biotechnological applications.
Folding in vivo is for many proteins assisted by several protein factors such as molecular chaperones. Although these proteins can fold spontaneously the chaperones suppress aggregation during folding and increase the yield. In our research we aim to gain insights into the mechanism of chaperone function that is essential for the understanding of the folding mechanism and prevention of misfolding.
Analysis of the ß-sheet propensity of amino acids are in progress using the blood coagulation factor Tissue Factor as a model protein to better understand how to rationally stabilize ß-sheet containing proteins. In addition, the stabilizing effects of additives are investigated to find biopharmaceutical formulations that will prolong the shelf-life of proteins.
Studies have also been initiated on the enzyme thiopurine methyltransferase (TPMT) which is a polymorphic enzyme and a key enzyme in treatment of childhood leukemia and inflammatory bowel diseases such as Crohn’s disease.
TPMT is one of the few classical examples of pharmacogenetics where the dosages of medical drugs are directly dependent on the polymorphism of the enzyme. TPMT are now cloned in E.coli and the effects of the mutations on the structure and function are investigated.
Responsible for this page: Maria Sunnerhagen
Last updated: 05/27/08