RTD Project Title: Folding structures and activity of engineered metalloproteins at high resolution

Contract N°: FMRX-CT98-0230

Name of Contract Manager : Prof. A.R. Fehrst

Contractual period : 01/04/98 to 31/03/2001

Partnership Summary

1 Medical Research Council, Centre for Protein Engineering, MRC.CPE, London, United Kingdom
2 Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine Paramagnetiche, CIRMMP.RMR, Florence, Italy
3 Lehrstuhl fur Biophisik, Ruhr-Universitat, UBOH.IBP, Bochum, Germany
4 Bijvoet Centre for Biomolecular Research, RUUTR.DBOC.R, Utrecht, The Netherlands
5 Instituto de Estructura de la Materia, CSIC.IEM, CSIC.IEM, Spain

PROJECT OVERVIEW

Understanding the factors controlling protein stability and folding is central to the ability to engineer biomolecules of desired function. There are two fundamental objectives behind this project. Firstly to extend the ability of Nuclear Magnetic Resonance (NMR) methods to obtain structural information from denatured and conformationally dynamic folded states of engineered metalloproteins. These methods will take advantage of the paramagnetic properties of the metallic centres in the protein to provide longer range structural constraints than are usually obtained by NMR methods. In addition to structural studies, 15N and 13C relaxation measurements will be applied and extended to provide dynamic information from conformationally 'active' proteins whose folding is dependent on cofactor binding, oxidation state and hydration.