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Neuropeptide Y receptor Y2 site-directed mutagenesis

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Neuropeptide Y receptor Y2 site-directed mutagenesis Jasna Pruner

During the past few years, the structural biology of G-protein-coupled-receptors has seen remarkable advances and crystallographic data for a number of receptors became available. This data offers valuable clues for constructing templates for computational 3D model building of receptors with unresolved structures such as for instance, the receptors in the neuropeptide Y family. Neuropeptide Y2 receptor is an attractive pharmacological target for anti-obesity medications due to its appetite suppressing properties in response to peptide YY

3-36

. Experimental attempts to design a peptidomimetic based on peptide YY

3-36

structure require a detailed structure of neuropeptide Y2 receptor. This degree project is a part of research project aiming to determine the properties of the Y2 receptor ligand-binding network by an integrated approach combining computational modeling and site-directed mutagenesis. Two docking solutions of the human neuropeptide Y to the Y2 receptor have revealed ligand binding positions that became the candidates for site-directed mutagenesis. The aim of this degree project is to introduce mutations Y

1.39

A, Q

6.55

L, Q

3.32

A, Q

3.32

L, H

7.39

A and H

7.39

L into the plasmids carrying the Y2 coding region. Preliminary tests indicate a binding loss in receptors carrying amino acid substitutions Q

6.55

L, Q

3.32

A, H

7.39

A and H

7.39

L. These results are consistent with the docking solutions we propose for the Y2 receptor.

Degree project in Biology, Master of Science (1 year), 2011 Examensarbete i biologi 15hp till magisterexamen, 2011

Biology Education Centre and Department of Neuroscience, Unit for Pharmacology, Uppsala University

Supervisor: Dan Larhammar

References

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