Professor David Craik Institute for Molecular Bioscience University of Queensland Brisbane, Qld 4072 Email: d.craik@imb.uq.edu.au Tel: +61-7-3346 2019 Fax: +61-3346 2029 Homepage: http://www.imb.uq.edu.au/index.html?id=11695 Research The structures, evolutionary origin and applications of protein-based protease inhibitors. The main focus is on plant based trypsin and chymotrypsin inhibitors. With Marilyn Anderson at La Trobe University we have been characterizing the structures of multi-domain proteins from N. alata, and tracing the evolutionary origin and the biophysical determinants of their unusual domain-swapped folding. In addition, we are elucidating the interactions of the plant proteinase inhibitors with insect proteases to develop novel strategies for crop protection against insect pests. The discovery of novel plant protease inhibitors and their application in drug design. We are exploiting SFTI-1 and MCoTI-II, both naturally occurring circular trypsin inhibitors from plants, as templates in drug design. We are also interested in the development of protease inhibitors against Alzheimers disease. The discovery of novel proteases involved in the processing of circular proteins The cyclotides are a novel family of plant-derived family of knotted, circular proteins. We are interested in the novel proteases involved in processing these products from their precursor proteins. Collaborations Associate Professor Marilyn Anderson, Biochemistry, La Trobe University Dr Horst Schirra, IMB, UQ Dr Ute Marx, University of Bayreuth, Germany Publications Schirra H J, Scanlon M J, Lee M C S, Anderson M A, Craik D J: The solution structure of C1-T1, a two-domain proteinase inhibitor derived from a circular precursor protein from Nicotiana alata. J Molecular Biology (2001) 36, 69-79. Rosengren K J, Daly N L, Scanlon M J, Craik D J: Solution structure of BSTI: A new trypsin inhibitor from skin secretions of Bombina bombina. Biochemistry. (2001) 40, 4601-4609. Felizmenio-Quimio M E, Daly N L, Craik D J: Circular proteins in plants: Solution structure of a novel macrocyclic trypsin inhibitor from Momordica cochinchinensis. J. Biol Chem. (2001) 276, 22875-22882. Korsinczky M L J, Schirra H J, Rosengren K J, West J, Condie B A, Otvos L, Anderson M A, Craik D J: Solution structures by 1H NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant. J. Mol. Biol. (2001) 311 579-591. Marx U C, Korsinczky M L J, Schirra H J, Jones A, Condie B, Otvos L, Craik D J: Enzymatic cyclisation of the potent Bowman-Birk protease inhibitor SFTI-1: Solution structure of linear precursor peptide. Journal of Biological Chemistry (2003) 278, 21782-21789. Questions/suggestions? Please contact the Network Administrator. Copyright © by International Protease Network All Right Reserved.