'Hidden domains’ offer clue to drug resistance

Associate Professor Helen Irving

Associate Professor Helen Irving

The Monash University study has revealed ‘hidden domains’ in plant receptor enzymes, which, if also found in microorganisms, could explain how some types of bacteria have been able to evolve drug resistance undetected.

A paper based on the study, led by Associate Professor Helen Irving from the Monash Institute of Pharmaceutical Sciences, has been published in the international Journal of Biological Chemistry.

Associate Professor Irving said the ‘hidden domains’ were discovered in a type of multifunctional receptor enzyme, known as phytosulfokine or PSK receptors.

“All living things are made up of groups of chemical compounds known as proteins. Some of these proteins, called enzymes, have catalytic activity and others are receptors. The catalysts ‘facilitate’ chemical reactions, while the receptors receive signals from other cells, which cause the proteins to do something in response,” Associate Professor Irving said.

“Sometimes enzymes, like the PSK receptors we investigated, can contain several functions and these multiple functions help to accelerate growth and development.”

“Prior to this study, the consensus had been that the architecture of a multifunctional enzyme separated its catalytic domains to different regions of the protein. What we discovered is that within PSK receptors there are actually two enzymes, which are practically overlapping.”

“The significance of this discovery is it means previous studies may have ‘missed’ identifying minor enzyme activity because, once one enzyme had been identified, there would have been no expectation of finding another within the same region, what we refer to as this kind of ‘hidden domain’.”

Associate Professor Irving said the study could provide insight into how different enzymes evolve in microorganisms, such as bacteria.

“These types of ‘hidden domains’ could be present in microorganisms. So now, if we know where to start looking, we might uncover clues as to how microbes are able to develop new ‘functions’, such as resistance to some drugs,” Associate Professor Irving said.

“Understanding how microbial proteins evolve to become drug resistant has proved extremely difficult and I suspect this could in part be due to the fact that we have not been able to see certain enzyme activity due to it taking place within ‘hidden domains’.”

Associate Professor Irving said her team has identified other plant enzymes that could contain these ‘hidden domains’ and is now broadening the research to investigate the new enzymes.