Multidisciplinary research done by Prof Albie van Dijk from the North-West University (NWU), in collaboration with researchers from other national and international institutions, is reminiscent of detectives solving a mystery – a 16-year-old one, to be specific.

Prof Albie, a veteran in molecular biology, of which protein research is an integral part, says the team was looking to solve the actual structure of the bovine glycine-N-acyltransferase (bGLYAT) enzyme. This is a type of protein involved in detoxification and metabolic diseases that the NWU’s Centre for Human Metabolomics has been researching for the past 16 years.

The recent collaborative research project with the University of the Free State (UFS) has brought them closer to solving the puzzle, and has also led to the honour of having their research findings published in the renowned international publication Science.

But why is this research significant?

Prof Albie explains that the importance of determining the first structure of a GLYAT enzyme lies in understanding how the protein functions. “Determining the three-dimensional structure of the enzyme and then identifying changes that affect its form or function help us to pinpoint why certain metabolic problems arise. It also helps us identify genetic variations in the proteins that can cause bottlenecks and knock-on effects in the metabolic path in which the enzyme is doing its work in animals and humans.”

Why proteins are potent

Every cell in the human body contains many proteins that are essential for growth and development. Various different proteins play important roles in maintaining health, and range from those that are messengers, such as hormones, to those that regulate the rate at which chemical reactions take place.

Understanding the intricate workings of proteins by determining their structure offers scientists and researchers opportunities to learn how to affect, modify or control these proteins, and in doing so, find solutions to pressing human problems that include severe tiredness, and the reasons why people stop growing. The accurate prediction of protein structures, which is important in developing medicine, treatment and vaccines, and the interactions of these structures have been a challenge for scientists and researchers for many years.

The work of the NWU and UFS researchers goes a long way towards solving the mystery of the three-dimensional atomic structure of the bGLYAT enzyme. Evidence of this is the inclusion of their latest findings in the July 2021 edition of the internationally respected journal Science.

International exposure

The journal published a collaborative paper led by researchers from the University of Washington (USA), with contributions from researchers at Harvard and Stanford universities and the University of Cambridge (UK), among other institutions. The publication reports the development of software that uses deep-learning artificial intelligence (AI) to accurately predict protein structures and their interactions. Some of the data used to test and validate the software program was from the work of Dr Ana Ebrecht, Prof Albie’s postdoctoral fellow, and Prof Dirk Opperman from the UFS.

How the success story started

Prof Albie says it is a great honour that the research findings have been shared in Science. “It is a shining example of multidisciplinary, multinational research that includes solid molecular protein expression and enzyme research from South Africa, the excellent structural data received from the synchroton in Oxford, and the UK and US computer software programs used in determining the structure.”

The collaboration started when Ana gave a presentation about the bGLYAT project at the Collaborative Computational Project number 4 (CCP4) Crystallographic School on protein crystallography from 22 February to 5 March this year. “Many of the lecturers were interested in the research and afterwards Prof Randy Read, a lecturer from the University of Cambridge, approached me, offering that we could use the recently developed software RoseTTAFold to solve our structure if they could, in turn, use our data to validate their program.”

The research is funded by the Global Challenges Research Fund Synchroton Techniques for African Research and Technology (GCRF-START) of the United Kingdom’s Science and Technology Facilities Council (STFC). To learn more about GCRF-START, visit https://start-project.org/home/about

Prof Albie says they are now starting to look rationally at the solved structure to obtain a model of human GLYAT and develop applications that may improve the quality of life of people with certain health conditions. “We are excited about the research possibilities that will result from this work and hope this is the start of more collaborations, locally and internationally.”

To read the research paper as it appeared in Science, visit: https://science.sciencemag.org/content/early/2021/07/19/science.abj8754

The core team of researchers and collaborators that contributed to the study published in Science are Prof Albie van Dijk, Prof Dirk Opperman and Dr Ana Ebrecht.