叶酸和甲氨蝶呤与干酪乳杆菌二氢叶酸还原酶复合物中多种构象和动态过程的3H核磁共振研究。
3H-n.m.r. studies of multiple conformations and dynamic processes in complexes of folate and methotrexate with Lactobacillus casei dihydrofolate reductase.
作者信息
Curtis N, Moore S, Birdsall B, Bloxsidge J, Gibson C L, Jones J R, Feeney J
机构信息
Chemistry Department, University of Surrey, Guildford, U.K.
出版信息
Biochem J. 1994 Oct 15;303 ( Pt 2)(Pt 2):401-5. doi: 10.1042/bj3030401.
[7,3',5'-3H3]- and [7,9-3H3]-folic acid and [7,3',5'-3H3]methotrexate (MTX) have been prepared and 3H-n.m.r. spectra obtained for their complexes with Lactobacillus casei dihydrofolate reductase (DHFR). The 3H results confirm the presence of three pH-dependent different conformational forms in the complex DHFR.NADP+.folate. The folate benzoyl ring could be shown to be in essentially the same environment in the different forms, with the major differences being associated with the pterin ring. The appearance of a single resonance for the 3',5'-tritons showed that the benzoyl ring is flipping rapidly in all three forms. In contrast, the MTX complex was shown to exist as a single conformational state with the benzoyl ring flipping rate being too low to give a single averaged signal for the 3',5'-nuclei over the temperature range 283-313 K.
已制备出[7,3',5'-³H₃]-和[7,9-³H₃]-叶酸以及[7,3',5'-³H₃]甲氨蝶呤（MTX），并获得了它们与干酪乳杆菌二氢叶酸还原酶（DHFR）形成的复合物的³H核磁共振谱。³H结果证实了在复合物DHFR·NADP⁺·叶酸中存在三种pH依赖性不同构象形式。叶酸苯甲酰环在不同形式中基本处于相同环境，主要差异与蝶呤环有关。³',5'-氚核的单一共振出现表明苯甲酰环在所有三种形式中都快速翻转。相比之下，MTX复合物显示为单一构象状态，苯甲酰环的翻转速率过低，在283 - 313 K温度范围内无法为³',5'-核给出单一平均信号。
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