Dr J. Mitchell Guss, Principal Research Fellow, School of Molecular and Microbial Biosciences, Sydney University.
Brief summary of expertise and significant research achievements:
The major focus of research in the laboratory for more than twenty years has
been the way in which the versatile properties of metal ions are exploited
by biological systems. The background to the work involved years of research
using so-called model compounds to study biological systems at a time when
experimental techniques were not available to study the
"real" systems.
Specific research themes
Copper amine oxidases: this family of homologous enzymes are found in all
three kingdoms of life. They carry out the same relatively simple chemical
reaction - oxidising organic amines to aldehydes. This reaction is used
however for a wide variety of biological functions. In bacteria and other
simple organisms the principal function of these enzymes is to provide a
source of nitrogen and carbon for metabolism. In plants the enzymes are
thought to be recruited to sites of tissue damage where they participate
in the wound healing process. In mammals copper amine oxidases perform a
wide variety of functions depending on the tissue location. These functions
include the catabolism of toxic amines, the crosslinking of connective
tissue and the formation of artherosclerotic plaques. We are conducting
structural studies with two broad aims. Firstly, to define the role of
the copper atom in the formation of the organic quinone cofactor and in
the enzyme mechanism. Secondly to provide a structural basis for the
specificities of individual enzymes with a long term view to designing
inhibitors which may act as drugs.
Enzymes with dincuclear metal sites: A large number of enzymes have been characterized which have a dinuclear metal cluster in their active sites. Despite having very active sites the enzymes performs a wide variety of functions and utilize different metal ions in their active forms. For example dihydroorotase, which performs an essential step in the synthesis of nucleic acids, has zinc in its active site. On the other hand despite having a very similar active site, prolidase - a proline-specific dipeptidase - is inactive in the presence of zinc but active in the presence of cobalt. We are interested in defining what makes enzymes specific for different metal ions and what differences the metals confer on the enzymes.
Blue' copper proteins: The first de novo protein structure solved in Australia was that of the 'blue' or 'type 1' copper protein plastocyanin. This family of proteins is characterized by spectroscopic and redox properties not normally observed in low molecular weight copper complexes. Since we published the original structure we have since solved the structures of plastocyanin from a number of different plants, algae and cyanobacteria and of other blue copper proteins. One of these, cucumber basic protein, was solved by the then novel method of multiple wavelength anomalous dispersion, which utilizes
International linkages:
Harry Gray (CalTech)
Dave Dooley (Montana State)
Paul Ellis (SSRL)
Michael Adams (University of Georgia, Athens)
William Simmons (Loyola Medical School, Chicago)
Students and postdocs likely to be involved in or use
the Network:
Dr Anthony Duff Human purple acid phosphatase
Dr Megan Maher Structures of prolidase
Stephen Graham (PhD student) Structures of aminopeptidase P
Dr A. Adams DNA/drug complexes
Ms Caroline Leong Topoisomerase
Dr David Langley Structures of Arthrobacter globiformis amine oxidase
Ms Mihwa Lee Structures of auracyanin
Relevant grants:
| 2003-2005 | A. Adams, J.M. Guss & W. Denny (Auckland) 'The structural basis for the action of anticancer DNA-intercalating topoisomerase poisons' 253619 |
| 2002-2004 | J.M. Guss & H.C. Freeman 'Structural studies of catalysis and electron transfer by copper proteins' (DP0208320) |
| 2002-2004 | J.M. Guss & H.C. Freeman 'Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase' (DP0209273) |
Selected Relevant publications:
Bond, C. S., Blankenship, R. E., Freeman, H. C., Guss, J. M., Maher,
M. J., Selvaraj, F. M., Wilce, M. C., and Willingham, K. M. (2001)
Crystal structure of auracyanin, a "blue" copper protein from the
green thermophilic photosynthetic bacterium Chloroflexus aurantiacus.
J. Mol. Biol. 306, 47-67.
Maher, J. M., Ghosh, M., Grunden, A. M., Menon, A. L.,
Adams, M. W. W., Freeman, H. C., and Guss, J. M. (2004) Structure
of the prolidase from Pyrococcus furiosus. Biochemistry accepted for publication.
Maher, J. M., Cross, M., Wilce, M. C. J., Guss, J. M., and Wedd, A. G. (2003)
Structures of metal-substituted derivatives of the rubredoxin from
Clostridium pasteurianum. Acta Cryst. Accepted for publication.
Duff, A. P., Cohen, A. E., Ellis, P. J., Kuchar, J. A., Langley,
D. B., Shepard, E. M., Dooley, D. M., Freeman, H. C., and Guss, J. M.
(2003) The crystal structure of Pichia pastoris lysyl oxidase.
Biochemistry In press.
Graham, S. C., Lee, M., Freeman, H. C., and Guss, J. M. (2003)
An orthorhombic form of Escherichia coli aminopeptidase P at 2.4 A
resolution. Acta Cryst. D59, 897-902.
