Seminar: | (322) Targeting branched chain amino acid biosynthesis for herbicides and antifungals |
Speaker: | Dr. Luke Guddat, Associate Professor, School of Chemistry and Molecular Biosciences, The University of Queensland, Australian |
Time: | 2018-09-25 15:30 to 2018-09-25 16:30 |
Venue: | Meeting room (406), Building 24 |
Organizer: |
Health Science Platform Abstract: Acetohydroxyacid synthase AHAS is the first enzyme in the branched chain amino acid biosynthesis pathway. This pathway is present only in plants, bacteria and fungi making it an excellent target for drug and herbicide discovery. In total, 50 commercial herbicides have been developed that target this enzyme and are now in world-wide use for crop protection. We have used X-ray crystallography and kinetic studies to show precisely the mode of action of these herbicides. Intriguingly, they act by a process of slow accumulative inhibition resulting in the modification of the enzymes’ cofactors ThDP and FAD and accelerate a side reaction leading to the production of peracetate . We have also shown that AHAS inhibitors are inhibitors of Candida albicans AHAS (Ki ~800 pM). In cell culture they have MIC values as low as 0.03 ug/mL.
Short CV Luke Guddat was awarded a PhD from Melbourne University and undertook postdoctoral studies at the University of Utah, Harrington Cancer Center in the USA and the Centre for Drug Design and Development (a precursor to the IMB) at UQ. In 2002, he joined the School of Chemistry and Molecular Biosciences at UQ as a group leader and has published over 135 peer reviewed scientific papers throughout his career. Three of his most recent papers describe advances that his group has made in the understanding of AHAS herbicide inhibition.
Further Information: Associate Professor Luke Guddat UQ School of Chemistry and Molecular Bioscience http://scmb.uq.edu.au/index.html UQ Science: The University of Queensland (UQ), Australia http://www.uq.edu.au/ |
Seminar: | (322) Targeting branched chain amino acid biosynthesis for herbicides and antifungals |
Speaker: | Dr. Luke Guddat, Associate Professor, School of Chemistry and Molecular Biosciences, The University of Queensland, Australian |
Time: | 2018-09-25 15:30 to 2018-09-25 16:30 |
Venue: | Meeting room (406), Building 24 |
Organizer: |
Health Science Platform Abstract: Acetohydroxyacid synthase AHAS is the first enzyme in the branched chain amino acid biosynthesis pathway. This pathway is present only in plants, bacteria and fungi making it an excellent target for drug and herbicide discovery. In total, 50 commercial herbicides have been developed that target this enzyme and are now in world-wide use for crop protection. We have used X-ray crystallography and kinetic studies to show precisely the mode of action of these herbicides. Intriguingly, they act by a process of slow accumulative inhibition resulting in the modification of the enzymes’ cofactors ThDP and FAD and accelerate a side reaction leading to the production of peracetate . We have also shown that AHAS inhibitors are inhibitors of Candida albicans AHAS (Ki ~800 pM). In cell culture they have MIC values as low as 0.03 ug/mL.
Short CV Luke Guddat was awarded a PhD from Melbourne University and undertook postdoctoral studies at the University of Utah, Harrington Cancer Center in the USA and the Centre for Drug Design and Development (a precursor to the IMB) at UQ. In 2002, he joined the School of Chemistry and Molecular Biosciences at UQ as a group leader and has published over 135 peer reviewed scientific papers throughout his career. Three of his most recent papers describe advances that his group has made in the understanding of AHAS herbicide inhibition.
Further Information: Associate Professor Luke Guddat UQ School of Chemistry and Molecular Bioscience http://scmb.uq.edu.au/index.html UQ Science: The University of Queensland (UQ), Australia http://www.uq.edu.au/ |