Receptor Structure and Function

Course objectives

To provide basic knowledge on receptor structure and receptor ligand-interactions and to introduce the participants to the fields of molecular biology and structure determination by protein crystallography. The course will take the participants from the gene to the three-dimensional crystal structure of a protein.

General contents and topics

Cellular communication relies on receptor-ligand interactions. It is therefore essential to gain a detailed structural knowledge of the receptor and the interactions with its ligands. The techniques of molecular biology in combination with X-ray structure determination constitute a strong and efficient tool for the elucidation of the questions concerning the interplay between a ligand or a potential drug and the receptor.

Molecular biological cloning approaches have provided the means to isolate genes and overexpress proteins. Heterologous expression systems are developed to optimise proper folding of the expressed proteins. Methods based on random and directed mutagenesis are instrumental in identifying protein-ligand interactions and characterise potential domains suitable for crystallisation.

X-ray crystallography is the most powerful experimental method for determining the three-dimensional structures of proteins. More than thousand different protein structures are known today, due to the progress in gene technology, in methods for X-ray data collection and in computer technology. The results have contributed decisively not only to the knowledge of the structure, but also to the knowledge of the biological function of proteins. It is therefore essential for researchers in many different fields within natural science to have a basic knowledge of how to analyse these results and apply them to their own scientific field.

The lectures will cover:

• Introduction to receptors
• Cloning and overexpression of proteins in various species
• Purification of receptor proteins and receptor purity/homogeneity tests
• Biochemical characterisation of receptors
• Crystallisation of receptor proteins
• Protein crystallography: data collection, phase determination, model building, refinements
• Structural analysis and databases
• Structure prediction (molecular modelling)
• State of the art 3D receptor structures

The practical exercises will cover:

• Isolation of overexpressed receptor protein and test for homogenous folding
• Receptor pharmacology
• Crystallisation of a protein and crystal handling
• Model building of a receptor protein from an electron density map
• Structural analysis of receptor proteins
• Search in databases (gene-, amino acid sequence, 3D structure etc.)

General information

The course will be organised as a one-week course and will comprise about 15 lectures and 15 hours of practical exercise.

Duration

15 to 19 April 2002.

Course weight

0.083 STÅ (STÅ = student full-time equivalent) = 4.98 ECTS (European Credit Transfer System).

Course director

Associate Professor Jette Sandholm Kastrup, Department of Medicinal Chemistry at The Royal Danish School of Pharmacy.

Course fee

Total: DKK 5,900 (including lunch),
of which operating costs amount to: DKK 1,900.
An additional amount for study materials: DKK 250.

Closing date for application

1 February 2002.

Course capacity

15 participants.

N.B.

The participants will be supplied with study materials composed of lecture notes or selected scientific publications.
Conditions for participation: The course is primarily offered to PhD students who have completed undergraduate courses in biochemistry, biology, chemistry, molecular biology, pharmacology, or pharmacy, or researchers within the pharmaceutical industry.

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