| 背景信息 |
Dihydrofolate reductase (DHFR) is a central enzyme in the folate metabolic pathway, essential for the de novo synthesis of purines, thymidylate, and specific amino acids. It catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, which serves as a vital one-carbon donor for the production of nucleic acid precursors required for DNA replication and cell proliferation. Structurally, DHFR contains a highly conserved active site that accommodates its substrate and cofactor, with flexible loops facilitating the hydride transfer process. Due to its indispensable role in cell division, DHFR is a primary target for antifolate chemotherapeutic agents, such as methotrexate, which competitively inhibit the enzyme to arrest the growth of rapidly dividing cancer cells. It is also the target of various antimicrobial agents, including trimethoprim. |