Three researchers from the University of Cape Town are being lauded for their innovative breakthrough in the structure of a group of enzymes, known as nitrilases. These enzymes have enormous biotechnological potential, according to UCT.
Using a technique called cryo-electron microscopy (cryo-EM), Jeremy Woodward, Andani Mulelu and Angela Kirykowicz were able to investigate the structure of the enzymes.
Jeremey Woodward, the principal investigator in UCT’s Structural Biology Research Unit said: “Enzymes produce all the chemicals in plants and animals that allow them to survive. They are the chemical factories of the cell. We found it really exciting to be able to open up the mechanism of this biological machine and understand it.”
Mulelu, who is currently a research scientist at the H3D Drug Discovery and Development Centre at UCT said, “We’re not just following nature. We are being inspired by it and altering what it can do. We are able to produce brand new enzymes.”
The impact of this research could be used to manufacturing better medicines and to clean up pollution.
Using nitrilases to make pharmaceuticals could revolutionise the way drug resistance is approached in Africa and other developing countries.
“The synthesis of chemicals using these enzymes could improve the drug discovery platform in Africa,” said Mulelu.
“Once you have hits you can optimise nitrilases for manufacturing of medicines,” added Woodward. He expanded on why the need for novel medicines is so great.
The technique of cryo-EM essentially determines the structure of large biological molecules. By adopting the technique, Woodward, Mulelu and Kirykowicz were able to produce the first high-resolution visualisation of a cryo-EM protein structure in Africa.
“By masking out a single helical turn [of the nitrilase] and treating this as a single particle, we were able to improve the resolution substantially,” the scientists explained in their paper published in Nature Research’s Communications Biology.
“This critical technology has only really been available for about five years. It’s an extremely sensitive detector that produces very, very sharp images,” said Woodward.
“Once we had the reconstruction, we were able to see what happened with the individual atoms and make a prediction about what would happen when we change those atoms.”
“It’s great to know that we are working on the cutting-edge and making an important contribution to science,” said Woodward. Mulelu said it gave them great confidence in their work.