Biomolecular NMR Professor Gottfried Otting

We develop and apply nuclear magnetic resonance (NMR) spectroscopy techniques to aid in development of pharmaceutical drugs.

Our group develops NMR methods for studying biological macromolecules such as proteins, DNA and protein-ligand complexes. We focus on methods for the rapid identification of protein-protein interaction sites and characterisation of ligand binding sites. NMR is also used to determine the three-dimensional structure of proteins and protein domains. Determining the structure of these molecules and complexes and relating it to their function is important for improving drug development.

Methods used include NMR spectroscopy, chemical synthesis, programming, and protein expression (in particular cell-free protein production).

Current research activities

Paramagnetic labelling of proteins

We have recently demonstrated that the binding mode of small ligand molecules on protein surfaces can be elucidated very rapidly with the help of paramagnetic NMR (for a review, see ref. 1). Furthermore, paramagnetic NMR provides a quick way of finding out how two protein molecules bind to each other in a protein-protein complex. We are currently developing novel methods of paramagnetic NMR, in particular new methods of site-specific attachment of lanthanide ions to gain rapid assignments of the protein NMR spectrum and structural information. We are also working on a new method of protein structure determination from paramagnetic NMR data.

Cell-free protein synthesis

The group extensively uses an in-house system for cell-free protein synthesis which allows the inexpensive preparation of selectively isotope-labelled proteins for NMR analysis (ref. 2). One of the system's great advantages is the possibility of NMR analysis without protein purification. In addition, we can use linear PCR-amplified DNA for the protein synthesis. It is possible to go from cDNA to protein NMR spectrum in 24 h and to introduce site-specific mutations on the way, if desired (ref. 3). We are also working on further improvements of the system.

3D structure of proteins

The 3D structures of proteins and protein domains of biological and medical interest are determined by NMR spectroscopy, including protein-protein and protein-DNA complexes.

Annual Research Report   (PDF format)

Group members

Academic Staff:
Professor Gottfried Otting   |   Dr Haobo Liang   |   Dr Karin Loscha   |   Dr Kiyoshi Ozawa   |   Dr Xun-Cheng Su

Technical and General Staff

PhD Students:
Dharshana Padmakshan     |   Peter Wu

Visiting Fellows:

Key publications

1. G. Pintacuda, M. John, X. C. Su, G. Otting. NMR structure determination of protein-ligand complexes by lanthanide labeling. Acc. Chem. Res. 40, 206-212 (2007).
2. K. Ozawa, P. S. C. Wu, N. E. Dixon, G. Otting. ¹⁵N-labelled proteins by cell free protein synthesis: strategies for high-throughput NMR studies of proteins and protein-ligand complexes. FEBS J. 273, 4154-4159 (2006).
3. P. S. C. Wu, K. Ozawa, S. P. Lim, S. Vasudevan, N. E. Dixon, G. Otting. Cell-free transcription/translation from PCR amplified DNA for high-throughput NMR studies. Angew. Chemie Int. Ed. 46, 3356-3358 (2007).
4. M. John, A. Y. Park, N. E. Dixon, G. Otting. NMR detection of protein 15N-spins near paramagnetic lanthanide ions. J. Am. Chem. Soc. 129, 462-463 (2007).
5. G. Pintacuda, A. Y. Park, M. A. Keniry, N. E. Dixon, G. Otting. Lanthanide labeling offers fast NMR approach to 3D structure determinations of protein-protein complexes. J. Am. Chem. Soc. 128, 3696-3702 (2006).

>>more publications

Group web page:  http://rsc.anu.edu.au/~go/ group photos

Professor G Otting Research School of Chemistry, Building 35 Australian National University Canberra ACT 0200 AUSTRALIA Ph: +61 2 6125 6507 Fx: +61 2 6125 0750 E-mail: go@rsc.anu.edu.au