Health
UQ researchers reveal three-dimensional structure of key enzymes
Researchers at the University of Queensland can unravel the mystery 50 years ago, leading to advanced herbicides and infectious disease treatments.
A research team led by Professor Luke Gooda of UQ has revealed a complete three-dimensional structure of the enzyme that provides the first step in the biosynthesis of three essential amino acids, leucine, valine, and isoleucine.
This is a major advance by scientists and has been pursued worldwide by chemists for half a century.
This information provides new insights into acetohydroxy acid synthase, a key enzyme that is the target of over 50 commercial herbicides.
It is also a potential target for new drugs to treat Infectious diseases such as tuberculosis Invasive Candida infection. “
Luke Gudat, Professor, University of Queensland
The team used advanced techniques such as cryo-electron microscopy and X-ray crystallography to decipher the fungal versions of plant structure and enzymes.
“We have identified how this very complex structure is assembled, which is a very unusual form of the Maltese cross,” said Professor Gooda.
“Coincidentally, the Maltese Cross also functions as part of the UQ logo.”
Professor Gooddad said the discovery could have significant implications for world agriculture.
“Sulfometuron is a herbicide that targets this enzyme and was widely used in the 1990s to protect wheat crops across Australia,” he said.
“But today it’s completely invalid because of the development of resistance.
“This new insight allows us to make changes to existing herbicides and restore future herbicide application options.”
Professor Goodatt said the enzyme only exists in plants and microorganisms, not in humans.
“For this reason, the herbicides and drugs of interest are likely to be safe and non-toxic for all mammals,” he said.
“And another surprising finding in the study was the role that a molecule known as ATP plays in the regulation of enzymes.
“Usually ATP plays a role in providing energy to all living cells,” said Goodatt.
“But here it behaves like an adhesive that holds the structure together.”
“They are a fascinating discovery for us and excited about new opportunities for targeted design of next-generation herbicides and antimicrobials.”
Most of the research was done by Dr. Thierry Ronienne and UQ PhD candidate Yu Shang Low.
Source:
See journal:
Ronienne, T. , other (2020) Structure of fungal and plant acetohydroxy acid synthases. Nature. doi.org/10.1038/s41586-020-2514-3..
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