Strength of axial water ligation in substrate-free cytochrome P450s is isoform dependent.
Strength of axial water ligation in substrate-free cytochrome P450s is isoform dependent.
复制标题
无底物细胞色素P450中轴向水结扎的强度取决于同工型。
DOI：
10.1021/bi401547j
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发表时间：
2014-03-11
期刊：
影响因子：
2.9
通讯作者：
Atkins, William M.
中科院分区：
文献类型：
--
作者：
Conner, Kip P.;Schimpf, Alina M.;Cruce, Alex A.;McLean, Kirsty J.;Munro, Andrew W.;Frank, Daniel J.;Krzyaniak, Matthew D.;de Montellano, Paul Ortiz;Bowman, Michael K.;Atkins, William M.
含血红素的细胞色素 P450 在静息状态下表现出异构体依赖性三价铁自旋平衡，并表现出差异底物依赖性自旋平衡。这些差异的基础尚不清楚。此处，磁性圆二色性 (MCD) 显示 CYP 3A4、2E1、2C9、125A1 和 51B1 的静息低自旋配体场存在显着差异，这表明轴向水连接到血红素的强度存在差异。专门对应于卟啉到金属的电荷转移转变的近红外波段的能量范围接近 2 kcal/mol。此外，实验确定的MCD能带与根据电子顺磁共振参数计算出的预期MCD能量并不完全一致，因此强调了实验数据的必要性。还测量了 500 至 680 nm 之间高自旋血红素的 MCD 标记带，表明这些异构体中高自旋 Cys(S–) → Fe3+ 转变的整体能量范围很窄。低自旋态 CYP 异构体之间轴向配体能量的差异可能有助于底物依赖性自旋态扰动的能量学。然而，这些配体场能与静息态酶中高自旋与低自旋的比例无关，这表明水接触血红素的差异或无底物高自旋状态中异构体依赖性差异。
The heme-containing cytochrome P450s exhibit isoform-dependent ferric spin equilibria in the resting state and differential substrate-dependent spin equilibria. The basis for these differences is not well understood. Here, magnetic circular dichroism (MCD) reveals significant differences in the resting low spin ligand field of CYPs 3A4, 2E1, 2C9, 125A1, and 51B1, which indicates differences in the strength of axial water ligation to the heme. The near-infrared bands that specifically correspond to charge-transfer porphyrin-to-metal transitions span a range of energies of nearly 2 kcal/mol. In addition, the experimentally determined MCD bands are not entirely in agreement with the expected MCD energies calculated from electron paramagnetic resonance parameters, thus emphasizing the need for the experimental data. MCD marker bands of the high spin heme between 500 and 680 nm were also measured and suggest only a narrow range of energies for this ensemble of high spin Cys(S–) → Fe3+ transitions among these isoforms. The differences in axial ligand energies between CYP isoforms of the low spin states likely contribute to the energetics of substrate-dependent spin state perturbation. However, these ligand field energies do not correlate with the fraction of high spin vs low spin in the resting state enzyme, suggestive of differences in water access to the heme or isoform-dependent differences in the substrate-free high spin states as well.
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