Researchers discover enzyme communication mechanism that could help drug development

In a study published in Advances in sciencethe Integrative Structural Biology team was able to identify a communication mechanism between the proteins that make up the complex enzymatic machinery that produces organic molecules, called natural products, with a wide range of disease-fighting properties.

The research is an important step in the search for new approaches to combating antimicrobial resistance, which will require new biologically active molecules – natural products – with antibacterial, antiviral or anticancer properties.

Scientists are continuously searching for new natural products, synthesized in microorganisms by enzymes, and testing them for suitable properties.

But scientists are also taking a different approach, trying to understand the enzyme mechanism themselves. These enzymes are known to be modular in nature, each module fitting in a specific way.

By better understanding how these modules fit together to create each specific natural product, scientists would be able to design or modify enzymes, which in turn would allow them to create new natural products or even it adjusts the existing ones already known. have useful properties.

Team leader Professor Teresa Carlomagno, Academic Director of the Henry Wellcome Building for Nuclear Magnetic Resonance University of Birmingham, said: “These enzymes are capable of producing a huge variety of bioactive substances that could be useful in drug discovery, however we do not fully understand the principles that govern how they work or how they are assembled. Our research provides a valuable step toward understanding and potentially exploiting these principles, which could help us design useful new enzymes.”

The team was able to use sophisticated structural biology equipment based in the Henry Wellcome Building for Nuclear Magnetic Resonance at the University of Birmingham. This allowed them to take a closer look at the dynamic communication processes within the enzyme machinery, which cannot be examined using other structural techniques such as X-ray crystallography because the processes are very dynamic.

Using the example of the anti-cancer drug Tomaymycin, the researchers showed how the two modules that make up the enzyme were able to “find” each other and join together to form the correct configuration.

“Although we are still far from being able to create new enzymes, this work opens up very exciting new possibilities for future research and is a step towards a new approach to drug discovery,” said Professor Carlomagno.