BSc (Monash University), PhD Melbourne University
Associate Professor
61 07 3365 3549
  • Research scientist and laboratory head School of Chemistry & Molecular Biosciences
  • Lecturer and course coordinator in biochemistry
  • Postgraduate coordinator in biochemistry
  • PhD obtained  from St Vincents Institute of Medical Research, Melbourne, Australia (1990)
  • Postdoctoral research University of Utah, and Harrington Cancer Center, USA (1991-1994)
  • Staff member The University of Queensland (1995-present)
  • Associate Professor, The University of Queensland (2010-present)
Brief Research Description: 
Protein structure and drug discovery
Research Focus and Collaborations: 

My fields of research are structural biology and rational drug design. The group uses X-ray crystallography and other physical measurements to determine how structure influences the function of enzymes. This knowledge allows us to rationally design and develop enzyme inhibitors that can act as therapeutic agents or herbicides. Four enzyme classes are being studied:

(i) those involved in nucleotide biosynthesis;
(ii) enzymes in the branched-chain amino acid biosynthesis pathway;
(iii) metalloenzymes and;
(iv) serine proteases in the blood clotting cascade.
Hypoxanthine-guanine phosphoribosyltransferase takes the naturally 6-oxopurines, hypoxanthine or guanine  and phosphoribosylpyrophosphate and converts these to the nucleotides  required for DNA/RNA synthesis. We are now targeting the Plasmodium falciparum and Plasmodium vivax enzymes to discover new inhibitors that we design to test as anti-malarial drugs.
We determined the three-dimesional structures of the catalytic subunit of plant, bacterial and fungal acetohydroxyacid acid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthetic pathway. In plants, this enzyme is the target for a number of commercial herbicides including members of the sulfonylurea and imidazolinone families. Two goals are:
(i) to use this data to discover new AHAS inhibitors as biocide leads and;
(ii) to determine the structure of the regulatory subunit of AHAS.
We have determined the structures of plant, and bacterial ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthetic pathway. The enzyme contains two closely spaced metals and NADPH and undergoes major structural changes during its catalytic cycle. We are currently investigating these structures. KARI’s position in the branched-chain biosynthesis pathway also makes it an attractive target to discover new biocides.
We have determined the structures of plant and animal purple acid phosphatase, a metalloenzyme with two closely spaced metal centres. Based on our latest structures we have proposed a detail mechanism of catalysis for this enzyme. Inhibitors of the animal enzyme are considered excellent anti-osteoporotic drug leads.
We are studying the structure and inhibition of the serine proteases, plasmin and plasma kallikrein, and their roles in the blood clotting cascade. Our group is discovering protease inhibitors within Australian snake venoms as potential therapeutic drug leads.
Funded Projects: 

An integrated approach to combat antibiotic resistance - NHMRC project - Guddat, Schenk, McGeary, Sidjabat 2015-2017

An integrated approach to antimalarial drug discovery-NHMRC-project- Guddat, Hockova, Edstein, Naesens, de Jersey 2012-2014

Acetohydroxyacid synthase: A target for antifungal therapy NHMRC-project Guddat, Wang, Fraser 2011-2013

  • BIOL1007: Molecular & Cellular Biology
  • BIOL1040: Cells to Organisms
  • BIOC3000: Advanced Biochemistry and Molecular Biology
  • BINF6001: Introduction to Proteins & Nucleic Acids
  • BIOC6007: Directed Studies in Biomolecular Structure & Function
  • BIOC7004: Advanced Protein Technology
Selected Publications: