Observation of an unusual electronically distorted semiquinone radical of PCB metabolites in the active site of prostaglandin H synthase-2.
Observation of an unusual electronically distorted semiquinone radical of PCB metabolites in the active site of prostaglandin H synthase-2.
复制标题
DOI：
10.1016/j.chemosphere.2010.08.041
复制
发表时间：
2010-12
期刊：
影响因子：
8.8
通讯作者：
Luthe G
中科院分区：
文献类型：
--
作者：
Wangpradit O;Moman E;Nolan KB;Buettner GR;Robertson LW;Luthe G
将空气中的多氯联苯代谢物活化成高活性自由基具有根本重要性。我们发现人重组前列腺素H合酶-2（hPGHS-2）通过单电子氧化将二羟基多氯联苯（4-氯联苯-2 ′，5 ′-氢醌（4-CB-2′，5 ′ H2 Q））转化为半醌自由基。利用电子顺磁共振（EPR）技术，观察到4-氯联苯-2 ′，5 ′-半醌自由基（4-CB-2 ′，5 ′-SQ·−）与4-CB-2 ′，5 ′-H2 Q形成对称的四重峰（面积比为1：3：3：1）.该光谱随时间变化为不对称光谱：这种变化可以解释为两种不同的半醌自由基物种的重叠。4-CB-2′，5 ′-SQ·−的受阻旋转似乎不是线形变化的主要因素，因为增加甘油介质的粘度不会导致线形发生显著变化。引入氟，这增加了旋转的二羟基PCB研究的空间位阻，也没有产生显着的变化。4-CB-2′，5 ′ H2 Q在hPGHS-2的过氧化物酶位点的计算机分子对接模型以及从头算量子力学研究表明，带负电荷的羧酸在过氧化物酶活性位点的紧密接近可能是导致光谱中观察到的扰动的原因。这项研究提供了新的见解，从PCB代谢物的半醌的形成，并强调PGHS-2在PCB的代谢活化的潜在作用。
The activation of the metabolites of airborne polychlorinated biphenyls (PCBs) into highly reactive radicals is of fundamental importance. We found that human recombinant prostaglandin H synthase-2 (hPGHS-2) biotransforms dihydroxy-PCBs, such as 4-chlorobiphenyl-2′,5′-hydroquinone (4-CB-2′,5′H2Q), into semiquinone radicals via one-electron oxidation. Using electron paramagnetic resonance (EPR) spectroscopy, we observed the formation of the symmetric quartet spectrum (1:3:3:1 by area) of 4-chlorobiphenyl-2′,5′-semiquinone radical (4-CB-2′,5′-SQ•−) from 4-CB-2′,5′H2Q. This spectrum changed to an asymmetric spectrum with time: the change can be explained as the overlap of two different semiquinone radical species. Hindered rotation of the 4-CB-2′,5′-SQ•− appears not to be a major factor for the change in lineshape because increasing the viscosity of the medium with glycerol produced no significant change in lineshape. Introduction of a fluorine, which increases the steric hindrance for rotation of the dihydroxy-PCB studied, also produced no significant changes. An in silico molecular docking model of 4-CB-2′,5′H2Q in the peroxidase site of hPGHS-2 together with ab initio quantum mechanical studies indicate that the close proximity of a negatively charged carboxylic acid in the peroxidase active site may be responsible for the observed perturbation in the spectrum. This study provides new insights into the formation of semiquinones from PCB metabolites and underscores the potential role of PGHS-2 in the metabolic activation of PCBs.
登录
查看更多内容
影响因子：
2.9
作者：
Carabaza, A;Cabre, F;Mauleon, D
通讯作者：
Mauleon, D
影响因子：
5.6
作者：
Gupta, K;Selinsky, BS;Loll, PJ
通讯作者：
Loll, PJ
影响因子：
2.9
作者：
HSIA, JC;WONG, LT;FELDHOFF, RC
通讯作者：
FELDHOFF, RC
影响因子：
64.8
作者：
Kurumbail, RG;Stevens, AM;Stallings, WC
通讯作者：
Stallings, WC
影响因子：
4.1
作者：
Amaro, AR;Oakley, GG;Robertson, LW
通讯作者：
Robertson, LW