Active site mechanics of liver microsomal cytochrome P-450.

Active site mechanics of liver microsomal cytochrome P-450.
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肝微粒体细胞色素 P-450 的活性位点力学。

DOI:
10.1016/0003-9861(86)90445-5
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发表时间:
1986
影响因子:
3.9
通讯作者:
McCarthy,MB
McCarthy,MB
中科院分区:
生物学3区
文献类型:
--
作者:
White,RE;McCarthy,MB

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测定了一组10对位取代的甲苯衍生物与纯化的兔肝微粒体P-450LM2相互作用的三个酶常数。这三个常数分别是羟化反应的催化速率常数(KCAT)、酶-底物复合体的表观解离常数(Kd)和底物结合平衡与自旋态平衡之间的相互作用能(Δgint)。甲苯底物的对位取代基有:氢、氟、溴、氯、碘、硝基、甲基、氰基、异丙基和叔丁基。酶常数与底物分子的几个物理常数之间存在线性自由能关系。这些关联对于经验预测和对活性中心化学和力学的洞察都是有用的。催化速率通过Hanschπ疏水常数和Hammettσ值的线性组合进行关联。与邻甲苯相比,8-甲苯的氢同位素效应(DV)为2.6ford8-甲苯,证实了在这一系列底物上氢的提取是部分限速的。表观离解常数可以用摩尔体积和π的线性组合来预测,而自旋态相互作用能最好地用Hanschπ疏水常数和介电常数的倒数的线性组合来预测。
For a set of 10para-substituted toluene derivatives, three enzymatic constants were determined describing their interaction with purified rabbit liver microsomalP-450LM2. The three constants were the catalytic rate constant (kcat) for hydroxylation, the apparent dissociation constant (Kd) for the enzyme-substrate complex, and the interaction energy (ΔGint) between the substrate-binding and spin-state equilibria. Thepara-substituents of the toluene substrates were: hydrogen, fluoro, bromo, chloro, iodo, nitro, methyl, cyano, isopropyl, and t-butyl. Linear free energy correlations were sought between the enzymatic constants and several physical constants of the individual substrate molecules. These correlations would be useful both for empirical prediction purposes and for insight into active site chemistry and mechanics. Catalytic rates were correlated by a linear combination of the Hansch π hydrophobic constant and the Hammett σ value. A deuterium isotope effect (DV) of 2.6 ford8-toluene compared tod0-toluene confirmed that hydrogen abstraction was partially rate-limiting with this series of substrates. Apparent dissociation constants were predicted by a linear combination of the molar volume and π, while the spin-state interaction energies were best predicted by a linear combination of the Hansch π hydrophobic constant and the reciprocal of the dielectric constant.
DOI: 10.1016/s0021-9258(17)43248-0
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
作者:
G. Miwa;J. Walsh;A. Y. Lu
通讯作者: A. Y. Lu
DOI: 10.1021/bi00531a026
发表时间: 1982-01-01
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
GELB, MH;HEIMBROOK, DC;SLIGAR, SG
通讯作者: SLIGAR, SG
DOI: 10.1016/s0021-9258(17)43882-8
发表时间: 1983-12
期刊: The Journal of biological chemistry
影响因子: --
作者:
G. Miwa;J. Walsh;G. L. Kedderis;P. Hollenberg
通讯作者: G. Miwa;J. Walsh;G. L. Kedderis;P. Hollenberg
含碘有机碳酸酯作为研究不透射线化合物
DOI: 10.1021/jm00234a002
发表时间: 1976
影响因子: 7.3
作者:
B. N. Newton
通讯作者: B. N. Newton
肌红蛋白与苯肼的反应:分子门挡。
DOI: 10.1021/bi00296a001
发表时间: 1984
期刊: Biochemistry
影响因子: 2.9
作者:
Ringe,D;Petsko,GA;Kerr,DE;OrtizdeMontellano,PR
通讯作者: OrtizdeMontellano,PR