Research Network for Metals in Medicine

 

 

Professor Gottfried Otting

Position: Professor, Chemistry

Affiliation: Research School of Chemistry, Australian National University

Postal Address:
Australian National University
Research School of Chemistry
Canberra, ACT 0200
AUSTRALIA

Phone: +61 (02) 6125 6507
Fax: +61 (02) 6125 0750
Email: Gottfried.Otting@anu.edu.au
Webpage: http://rsc.anu.edu.au/~go/

Research Profile

Dr Otting’s research career has centred on the development of high-resolution NMR techniques for the study of biomolecular macromolecules in aqueous solution, their application in 3D structure determinations of proteins and protein/DNA complexes, and the measurement of biophysical parameters by NMR spectroscopy. While in the group of Prof K. Wüthrich at the ETH-Zürich, Switzerland, he invented a number of NMR techniques that significantly enhanced the use of two-dimensional NMR spectroscopy for protein analysis, including the suppression of t1-ridges in NOESY spectra, the development of half-filter techniques, the detection of protein hydration water in solution, and techniques for coupling constant measurements. Furthermore, he was involved in several 3D structure determinations, including the cobra toxin CTXIIb, the Antennapedia homeodomain (free and in complex with DNA), the P22 c2 repressor N-terminal DNA-binding domain, the DNA-binding fragment 195-286 of the LFB1/HNF1 transcription factor, and an artificial hexose DNA-analogue, ddGlc(A5T5).

Since his appointment at the Karolinska Institute, he continued work on the development of NMR techniques and on 3D structure determinations. Methods developed include homonuclear band-selective decoupling, rapid measurement of HN-Ha coupling constants, spin-state selective subspectral editing, sensitivity-enhanced TROSY, and sign determination of small coupling constants. 3D structure determinations included a Zn-finger (ZF-1), NK-lysin, the death domain of the p75 neurotrophin receptor, the DNA-binding domain of the E. coli arginine repressor, E. coli glutaredoxin-3 in complex with glutathione, the FMN-binding protein from Desulfovibrio vulgaris, the E. coli DnaB N-terminal domain, ERp29, the LCCL domain, a mutant AFP I peptide and AmpD. His current focus of interest is on natural metal binding sites of proteins, engineered metal binding sites and the use of paramagnetic metal ions for protein structure determination and the elucidation of the three-dimensional structure of protein-protein and protein-ligand complexes.

Selected Publications

  1. G. Pintacuda, M. A. Keniry, T. Huber, A. Y. Park, N. E. Dixon, G. Otting Fast structure-based assignment of 15N-HSQC spectra of selectively 15N-labeled paramagnetic proteins J. Am. Chem. Soc., in press
  2. E. Liepinsh, R. Barbals, E. Dahl, A. Sharipo, E. Staub, G. Otting Death-domain fold of ASC PYRIN domain, presenting a basis for PYRIN/PYRIN recognition J. Mol. Biol. 332, 1155-1163 (2003)
  3. G. Pintacuda, K. Hohenthanner, G. Otting, N. Müller Angular dependence of dipole-dipole Curie spin cross-correlation effects in high-spin and low-spin paramagnetic myoglobin J. Biomol. NMR 27, 115-132 (2003)
  4. E. Liepinsh, L. Banyai, G. Pintacuda, M. Trexler, L. Patthy, G. Otting NMR structure of the netrin-like domain of human type I procollagen C-proteinase enhancer defines structural conservation of NTR domains and assesses potential proteinase inhibitory activity and ligand binding J. Biol. Chem. 278, 25982-25989 (2003)
  5. E. Liepinsh, C. Genereux, D. Dehareng, B. Joris, G. Otting NMR structure of Citrobacter freundii AmpD, comparison with T7 lysozyme and homology with PGRP domains J. Mol. Biol. 327, 833-842 (2003)
  6. E. Liepinsh, A. Leonchiks, A. Sharipo, L. Guignard, G. Otting Solution structure of the R3H domain from human Smbp-2 J. Mol. Biol. 326, 217-223 (2003)
  7. L. Guignard, K. Ozawa, S. E. Pursglove, G. Otting, N. E. Dixon NMR analysis of in vitro-synthesized proteins without purification: a high-throughput approach FEBS Lett. 524, 159-162 (2002)
  8. G. Pintacuda, G. Otting Identification of protein surfaces by NMR measurements with a paramagnetic Gd(III) chelate J. Am. Chem. Soc. 124, 372-373 (2002)
  9. P. B. Crowley, G. Otting, B. G. Schlarb-Ridley, G. W. Canters, M. Ubbink Hydrophobic interactions in a cyanobacterial plastocyanin-cytochrome f complex J. Am. Chem. Soc. 123, 10444-10453 (2001)
  10. E. Liepinsh, M. Baryshev, A. Sharipo, M. Ingelman-Sundberg, G. Otting, S. Mkrtchian Thioredoxin-fold as a homodimerization module in the putative chaperone ERp29: NMR structures of the domains and experimental model of the 51 kDa homodimer Structure 9, 457-471 (2001)

Facilities

  • Varian 600 MHz NMR spectrometer
  • Bruker 800 MHz NMR spectrometer

International Linkages

Member of the EU network on Cross-Correlation (coordinated from Paris, France)
Edvards Liepinsh (Karolinska Institute, Sweden)
Anatoly Sharipo (University of Latvia)
Laszlo Patthy (Hungarian Academy of Science, Budapest)
Junji Sagara (Shinshu University, Nagano, Japan)