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

叶酸和甲硫氨酸循环是细胞存活的关键代谢途径。MTHFR酶代表了这些周期之间的关键调节连接，因此对一系列疾病产生了强烈的影响。MTHFR功能丧失或降低导致称为高胱氨酸尿症的危及生命的代谢紊乱，而另一方面，在某些癌症（例如前列腺）中观察到MTHFR的过表达。通过化学合成，生物物理测定，计算机对接和晶体学的组合方法，该项目旨在开发概念化学探针的证据，以调节MTHFR并探索两者的治疗潜力，抑制和激活酶。

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.