Champness J N, Stammers D K, Beddell C R
FEBS Lett. 1986 Apr 7;199(1):61-7. doi: 10.1016/0014-5793(86)81224-8.
The structure of the complex between E. coli (RT500) form I dihydrofolate reductase, the antibacterial trimethoprim and NADPH has been determined by X-ray crystallography. The inhibitor and cofactor are in mutual contact. A flexible chain segment which includes Met 20 is in contact with the inhibitor in the presence of NADPH, but more distant in its absence. By contrast, the inhibitor conformation is little changed with NADPH present. We discuss these observations with regard to the mutually cooperative binding of these ligands to the protein, and to the associated enhancement of inhibitory selectivity shown by trimethoprim for bacterial as opposed to vertebrate enzyme.
通过X射线晶体学确定了大肠杆菌（RT500）I型二氢叶酸还原酶、抗菌药物甲氧苄啶和NADPH之间复合物的结构。抑制剂和辅因子相互接触。在存在NADPH的情况下，包含甲硫氨酸20的柔性链段与抑制剂接触，但在不存在NADPH时距离更远。相比之下，存在NADPH时抑制剂的构象变化很小。我们就这些配体与蛋白质的相互协同结合以及甲氧苄啶对细菌酶而非脊椎动物酶所表现出的相关抑制选择性增强来讨论这些观察结果。
