A research team led by scientists at Obafemi Awolowo University (OAU), Ile-Ife, has achieved a significant milestone in malaria research by determining and depositing the first-ever crystal structure of Plasmodium falciparum transketolase bound to an inhibitor in the global Protein Data Bank (PDB).
The breakthrough marks the first Protein Data Bank structure authored entirely by Nigerian scientists, positioning the country as a direct contributor — rather than just a user — of high-level structural biology data.
Breaking a Long-Standing Scientific Barrier
The research was carried out at the laboratory of Olatomide Fadare, an Associate Professor of Chemistry at OAU. Originally trained as a synthetic organic chemist, Fadare has expanded into medicinal chemistry, integrating organic synthesis, bioinformatics and biological evaluation to design next-generation antimalarial drug candidates.
At the centre of the study is transketolase, a critical enzyme in Plasmodium falciparum, the parasite responsible for the deadliest form of malaria. For years, global efforts to design drugs targeting this enzyme were constrained by the absence of experimentally determined crystal structures, forcing researchers to rely largely on computational models.
“That barrier has now been broken,” Fadare said. “We carried out protein engineering, produced the protein and successfully crystallised it. Getting to the point where you can create a crystal from your protein is highly advanced science.”
The PDB serves as the world’s primary repository for experimentally determined protein structures, historically dominated by contributions from Western institutions.
“You rarely find deposits from Africa,” Fadare noted. “But now, instead of being users, we have become depositors.”
A Response to Drug Resistance
The research comes amid growing resistance to artemisinin-based combination therapies, currently the frontline treatment for malaria.
“If we don’t continue to design new therapies that target different pathways, the parasite will always catch up with us,” Fadare said, referencing the historical pattern of resistance seen with previous treatments such as Fansidar.
The team’s structural breakthrough now enables rational drug design targeting transketolase, opening a new therapeutic pathway.
Dr Olatomide Dare
Global Nigerian Collaboration
The project was executed through a network of Nigerian scientists across multiple institutions, including:
- University of Dundee
- Mount Sinai Hospital
- Covenant University
- Fayetteville State University
While Fadare’s laboratory in Ile-Ife designed and synthesised new chemical entities, collaborators abroad handled cloning, protein expression, crystallisation, inhibition assays, protocol optimisation and structural analysis.
“We are running interconnected projects across Nigeria, the UK, Canada and the US,” he said. “This positions Nigeria as a serious contributor to next-generation antimalarial drug discovery.”
Promising Drug Leads Identified
Beyond solving the enzyme’s structure, the team has already identified four to five small molecules that strongly inhibit the parasite’s transketolase without significantly affecting the human equivalent.
“Humans also express transketolase. The difference between the human and parasite enzymes is small but significant — significant enough to exploit,” Fadare explained. “It is possible to design a selective inhibitor that targets the parasite without harming the human host.”
The next phase will involve optimising these lead compounds to improve potency and specificity before advancing to further preclinical development.
Call for Investment in African Science
Fadare used the breakthrough to highlight broader systemic challenges facing African science, particularly heavy reliance on imported medicines and limited pharmaceutical manufacturing capacity.
“Virtually every active pharmaceutical ingredient used in Nigeria is imported, mostly from India or China,” he said. “We have the scientific expertise to produce them locally, but the industry has not matured to that level.”
He also raised concerns about brain drain, noting that many highly trained scientists leave due to limited industrial and funding opportunities.
“What happens in science translates directly into solutions in the health sector. Long-term, constructive investment in research is what produces breakthroughs,” he said.
Despite operating without dedicated government or institutional funding, Fadare’s team continues to advance its work. He believes that with sustained support, the laboratory could help catalyse a transformation in Nigeria’s pharmaceutical landscape.
“With the right support, what we are doing can cause a tectonic shift in the pharmaceutical industry,” he said. “If we get the right support, the impact will be massive.”