Developing novel chemical probes to interrogate the allosteric mechanism of MTHFR and explore its therapeutic potential

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The folate and methionine cycles are critical metabolic pathways for cell survival. The enzyme MTHFR represents a key regulatory connection between these cycles, hence exerting a strong influence on an array of diseases. Loss or reduced MTHFR function results in a life-threatening metabolic disorder called homocystinuria whilst on the other hand, overexpression of MTHFR has been observed in certain cancers (e.g. prostate). Through combined approaches of chemical synthesis, biophysical assays, in silico docking and crystallography, this project looks to develop proof of concept chemical probes to modulate MTHFR and explore the therapeutic potential of both, inhibiting and activating the enzyme.