Professor Tony Wedd
BSc(Tas.) PhD(Tas.) DSc(Tas.) FRACIS
Position: Professor of Chemistry
Affiliation: University of Melbourne
Over 140 original research publications in refereed international journals, books and encyclopediae; a high citation level of published work, including four "citation classics";inaugural Council Member, Society of Biological Inorganic Chemistry, 1997-1999; inaugural Member, Editorial Advisory Board, Journal of Biological Inorganic Chemistry, 1997-1999, 2002-; plenary or invited lecturer at the 7th, 8th and 10th International Conferences on Biological Inorganic Chemistry (the major conference serving that research area); Chair, 11th International Conference on Biological Inorganic Chemistry, Cairns, Australia, July 19-23, 2003; Program Chair, IC03, the conference of the Inorganic Division of the Royal Australian Chemical Institute, Melbourne, 2003; plenary lecturer at the International Symposium on Bioinorganic Chemistry, Mumbai, India, 2000; invited speaker, RACI National Convention, Canberra, 2000; invited graduate course on biological inorganic chemistry, University of Florence, Italy, 2001; invited lecturer, opening of Centre for Metals in Biology, University of Queensland, 2001; plenary lecturer, 1st Asian Meeting on Bioinorganic Chemistry, Kyoto, Japan, 2003; editor, Volume 4 (early transition metals) of the encyclopedia Comprehensive Coordination Chemisty 2, Elsevier, 2003; referee of 30 manuscripts in 2002, including 13 for JACS , Biochemistry or JCS Chem. Commun.; member, Chemistry Panel, Australian Research Council, 1998-2000; reader, Physics Chemistry and Geoscience Panel, Australian Research Council, 2001-4.
The common theme in the bio-metal work is the characterisation of individual proteins or metabolic pathways at the molecular level. In addition, I have an established presence in polyoxometalate anion redox chemistry and photo-chemistry.
Specific research themes
Molybdenum chemistry and biochemistry. (see Feature Article, J.C.S. Chem. Commun., 1997, 1251-1257 and refs therein). One aspect involved the first characterization of [MoVO2]+, [MoVOS]+, [MoVO(OH)]2+, [MoVO(SH)]2+ centers in synthetic species and their confirmation as intermediates in enzyme cycles (in particular, in xanthine oxidase isolated in his laboratory). A second aspect was synthesis of the first model combining oxygen atom transfer and coupled electron–proton transfer reactions representing, respectively, the substrate redox reaction and regeneration of the active site. More recently, photodetachment photoelectron spectroscopy was used to investigate the electronic structure of the doubly-charged complexes [MIVO(mnt)2]2- (M = Mo, W; mnt = 1,2-dicyanoethenedithiolato), providing detailed information about molecular orbital energy levels of the parent dianions as well as the ground and excited states of the product anions [MVO(mnt)2]- (J. Amer. Chem. Soc. 2004, accepted for publication). Overall, this study indicates that the electronic structure of the M-dithiolene units in molybdopterin cofactors are exquisitely sensitive to dithiolene ligand folding, reinforcing the proposal that these units are tunable conduits for electron transfer in enzyme systems.
Iron-sulfur proteins. Active sites have been probed by site-directed mutagenesis to vary first and second coordination spheres. This has provided new chemistry and probed the determinants of reduction potential (see J. Amer. Chem. Soc. 1998, 120, 4135-4150 and J. Biol. Inorg. Chem. 2001, 6, 638-649). In particular, different [Fe(S-Cys)3(O-Ser)] and [Fe(S-Cys)3(OH)] centers have been at the [Fe(S-Cys)4] site of rubredoxin. Unstable [FeIII(S-Cys)3(OH)] centers appear to be present in certain forms of NifU and IscU, proteins responsible for assembly and repair of iron-sulfur clusters in all biological cells (see J. Biol. Inorg. Chem., 2002, 7, 781-790).
Molecular basis of copper nutrition. A number of proteins are under study. The membrane pump Ctr1 is proposed as the primary port for copper import into mammalian cells and its function is essential for embryonic development in mice. An intriguing recent development has identified human Ctr1 as the primary entry point of the cancer drug cis-platin into human cells. This laboratory has provided the first molecular characterisation of a domain of a Ctr1protein (see J. Chem. Soc. Chem. Commun. 2002, 588-589 and J. Amer. Chem. Soc. 2004, accepted for publication). The hydrophilic cysteine-rich C-terminal domain of yeast Ctr1was expressed in soluble form and bound four copper atoms as a [CuI4(m-S-Cys)6]2- cluster of D2d local point symmetry. An idealised tetrahedron of Cu atoms is bound by an octahedron of bridging thiolates, one above each of the six edges of the tetrahedron. In vitro, it was able to deliver Cu(I) directly to both the chaperone Atx1 and to a soluble N-terminal domain of the Ccc2 protein (the Menkes and Wilson disease homologues of yeast). Each of the latter proteins feature mononuclear Cys-S-CuI-S-Cys binding sites. These three proteins are proposed to constitute the delivery pathway from the plasma membrane to the Golgi apparatus. In addition, all three were shown to buffer Cu(I) concentration at 10-19 M, consistent with the provocative proposal that, to eliminate toxicity, “free” copper concentrations in the cytosol are extremely low.
Laboratory equipped for isolation and quantitative study of highly purified metallo-proteins including site-directed mutagenesis and anaerobic handling facilities. Protein electrochemistry equipment.
Prof. Graham George (University of Saskatchewan, Canada)