19F核磁共振研究3',5'-二氟甲氨蝶呤与干酪乳杆菌二氢叶酸还原酶的结合。分子运动及辅酶诱导的构象变化。
19F-n.m.r. studies of 3',5'-difluoromethotrexate binding to Lactobacillus casei dihydrofolate reductase. Molecular motion and coenzyme-induced conformational changes.
作者信息
Clore G M, Gronenborn A M, Birdsall B, Feeney J, Roberts G C
出版信息
Biochem J. 1984 Feb 1;217(3):659-66. doi: 10.1042/bj2170659.
Abstract
19F-n.m.r. spectroscopy was used to study the binding of 3',5'-difluoromethotrexate to dihydrofolate reductase (tetrahydrofolate dehydrogenase) from Lactobacillus casei. The benzoyl ring of the bound difluoromethotrexate was found to 'flip' about its symmetry axis, and the rate (7.3 X 10(3) s-1 at 298 K) and activation parameters for this process were determined by lineshape analysis of the 19F-n.m.r. spectrum at a series of temperatures in the range 273-308 K. The contributions to the barrier for this process are discussed. Addition of NADP+ or NADPH to form the enzyme-difluoromethotrexate-coenzyme ternary complex led to an increase in the rate of benzoyl ring flipping by a factor of 2.6-2.8-fold, and to substantial changes in the 19F-n.m.r. chemical shifts. The possible nature of the coenzyme-induced conformational changes responsible for these effects is discussed.
摘要
利用19F核磁共振光谱研究了3',5'-二氟甲氨蝶呤与干酪乳杆菌二氢叶酸还原酶（四氢叶酸脱氢酶）的结合情况。发现结合态二氟甲氨蝶呤的苯甲酰环绕其对称轴“翻转”，通过对273 - 308 K范围内一系列温度下的19F核磁共振谱进行线形分析，确定了该过程的速率（298 K时为7.3×10³ s⁻¹）和活化参数。讨论了该过程中势垒的贡献。添加NADP⁺或NADPH形成酶 - 二氟甲氨蝶呤 - 辅酶三元复合物，导致苯甲酰环翻转速率增加2.6 - 2.8倍，并使19F核磁共振化学位移发生显著变化。讨论了辅酶诱导的构象变化导致这些效应的可能性质。
相似文献
1
19F-n.m.r. studies of 3',5'-difluoromethotrexate binding to Lactobacillus casei dihydrofolate reductase. Molecular motion and coenzyme-induced conformational changes.19F核磁共振研究3',5'-二氟甲氨蝶呤与干酪乳杆菌二氢叶酸还原酶的结合。分子运动及辅酶诱导的构象变化。
Biochem J. 1984 Feb 1;217(3):659-66. doi: 10.1042/bj2170659.
2
A 1H n.m.r. study of the role of the glutamate moiety in the binding of methotrexate to Lactobacillus casei dihydrofolate reductase.一项关于谷氨酸部分在甲氨蝶呤与干酪乳杆菌二氢叶酸还原酶结合中作用的核磁共振氢谱研究。
Br J Pharmacol. 1984 Feb;81(2):309-15. doi: 10.1111/j.1476-5381.1984.tb10080.x.
3
Structural comparisons of complexes of methotrexate analogues with Lactobacillus casei dihydrofolate reductase by two-dimensional 1H NMR at 500 MHz.采用500兆赫二维氢核磁共振技术对甲氨蝶呤类似物与干酪乳杆菌二氢叶酸还原酶复合物进行结构比较。
Biochemistry. 1987 Dec 29;26(26):8585-90. doi: 10.1021/bi00400a014.
4
Multinuclear NMR characterization of two coexisting conformational states of the Lactobacillus casei dihydrofolate reductase-trimethoprim-NADP+ complex.干酪乳杆菌二氢叶酸还原酶-甲氧苄啶-NADP⁺复合物两种共存构象状态的多核核磁共振表征
Biochemistry. 1984 Sep 25;23(20):4733-42. doi: 10.1021/bi00315a032.
5
Dihydrofolate reductase from amethopterin-resistant Lactobacillus casei. Effects of pH, salts, temperature, and source of NADPH on enzyme activity and substrate specificity studies.来自抗氨甲蝶呤干酪乳杆菌的二氢叶酸还原酶。pH值、盐类、温度以及NADPH来源对酶活性的影响和底物特异性研究。
Arch Biochem Biophys. 1977 Jun;181(2):569-79. doi: 10.1016/0003-9861(77)90263-6.
6
Characterization of rates of ring-flipping in trimethoprim in its ternary complexes with Lactobacillus casei dihydrofolate reductase and coenzyme analogues.甲氧苄啶与干酪乳杆菌二氢叶酸还原酶及辅酶类似物形成的三元复合物中环翻转速率的表征。
Biochemistry. 1999 Nov 30;38(48):15962-9. doi: 10.1021/bi9915263.
7
N.m.r. studies of coenzyme binding to Lactobacillus casei dihydrofolate reductase.
Biochem Soc Trans. 1989 Apr;17(2):297-9. doi: 10.1042/bst0170297.
8
Interpretation of nuclear magnetic resonance spectra for Lactobacillus casei dihydrofolate reductase based on the X-ray structure of the enzyme-methotrexate-NADPH complex.基于干酪乳杆菌二氢叶酸还原酶-甲氨蝶呤-NADPH复合物的X射线结构对其核磁共振谱的解读
Biochemistry. 1979 Apr 17;18(8):1602-10. doi: 10.1021/bi00575a035.
9
3H-n.m.r. studies of multiple conformations and dynamic processes in complexes of folate and methotrexate with Lactobacillus casei dihydrofolate reductase.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。
Biochem J. 1994 Oct 15;303 ( Pt 2)(Pt 2):401-5. doi: 10.1042/bj3030401.
10
Dihydrofolate reductase: specificity and conformational change.
Biochem Soc Trans. 1987 Aug;15(4):762-6. doi: 10.1042/bst0150762.
引用本文的文献
1
F Magic Angle Spinning NMR Spectroscopy and Density Functional Theory Calculations of Fluorosubstituted Tryptophans: Integrating Experiment and Theory for Accurate Determination of Chemical Shift Tensors.氟代色氨酸的魔角旋转 NMR 光谱和密度泛函理论计算：实验与理论的结合，实现化学位移张量的精确测定。
J Phys Chem B. 2018 Jun 14;122(23):6148-6155. doi: 10.1021/acs.jpcb.8b00377. Epub 2018 May 30.
2
Structure and dynamics in solution of the complex of Lactobacillus casei dihydrofolate reductase with the new lipophilic antifolate drug trimetrexate.干酪乳杆菌二氢叶酸还原酶与新型亲脂性抗叶酸药物三甲曲沙复合物在溶液中的结构与动力学
Protein Sci. 1999 Mar;8(3):467-81. doi: 10.1110/ps.8.3.467.
3
3H-n.m.r. studies of multiple conformations and dynamic processes in complexes of folate and methotrexate with Lactobacillus casei dihydrofolate reductase.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。
Biochem J. 1994 Oct 15;303 ( Pt 2)(Pt 2):401-5. doi: 10.1042/bj3030401.
4
Dynamics of trimethoprim bound to dihydrofolate reductase.甲氧苄啶与二氢叶酸还原酶结合的动力学
Proc Natl Acad Sci U S A. 1988 Jun;85(11):3787-91. doi: 10.1073/pnas.85.11.3787.
5
The study of conformational states of proteins by nuclear magnetic resonance.通过核磁共振研究蛋白质的构象状态。
Biochem J. 1985 Oct 1;231(1):1-10. doi: 10.1042/bj2310001.
本文引用的文献
1
Crystal structure of avian dihydrofolate reductase containing phenyltriazine and NADPH.含苯基三嗪和烟酰胺腺嘌呤二核苷酸磷酸的禽源二氢叶酸还原酶的晶体结构
J Biol Chem. 1982 Mar 10;257(5):2528-36.
2
The internal dynamics of globular proteins.球状蛋白质的内部动力学。
CRC Crit Rev Biochem. 1981;9(4):293-349. doi: 10.3109/10409238109105437.
3
Protein dynamics by solid-state NMR: aromatic rings of the coat protein in fd bacteriophage.通过固态核磁共振研究蛋白质动力学：fd噬菌体外壳蛋白的芳香环
Proc Natl Acad Sci U S A. 1982 Jan;79(1):101-5. doi: 10.1073/pnas.79.1.101.
4
Characterization of the distribution of internal motions in the basic pancreatic trypsin inhibitor using a large number of internal NMR probes.使用大量内部核磁共振探针表征碱性胰蛋白酶抑制剂内部运动的分布情况。
Q Rev Biophys. 1983 Feb;16(1):1-57. doi: 10.1017/s0033583500004911.
5
Immunopharmacology of gold.金的免疫药理学
Prog Med Chem. 1982;19:1-58. doi: 10.1016/s0079-6468(08)70327-8.
6
7
Negative cooperativity between folinic acid and coenzyme in their binding to Lactobacillus casei dihydrofolate reductase.亚叶酸和辅酶在与干酪乳杆菌二氢叶酸还原酶结合过程中的负协同效应。
Biochemistry. 1981 Dec 8;20(25):7186-95. doi: 10.1021/bi00528a021.
8
Hydrogen-1 nuclear magnetic resonance study of the complexes of two diastereoisomers of folinic acid with dihydrofolate reductase.亚叶酸两种非对映异构体与二氢叶酸还原酶复合物的氢-1核磁共振研究。
Biochemistry. 1981 Mar 31;20(7):1837-42. doi: 10.1021/bi00510a019.
9
Effects of coenzyme binding on histidine residues of Lactobacillus casei dihydrofolate reductase.辅酶结合对干酪乳杆菌二氢叶酸还原酶组氨酸残基的影响。
Biochemistry. 1981 Mar 31;20(7):1717-22. doi: 10.1021/bi00510a003.
10
Effects of coenzyme analogues on the binding of p-aminobenzoyl-L-glutamate and 2,4-diaminopyrimidine to Lactobacillus casei dihydrofolate reductase.辅酶类似物对对氨基苯甲酰-L-谷氨酸和2,4-二氨基嘧啶与干酪乳杆菌二氢叶酸还原酶结合的影响。
Biochemistry. 1980 Aug 5;19(16):3732-7. doi: 10.1021/bi00557a014.
Zotero 插件