کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5746590 1618803 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structural-functional adaptations of porcine CYP1A1 to metabolize polychlorinated dibenzo-p-dioxins
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست شیمی زیست محیطی
پیش نمایش صفحه اول مقاله
Structural-functional adaptations of porcine CYP1A1 to metabolize polychlorinated dibenzo-p-dioxins
چکیده انگلیسی


- Five PCDDs differing in toxicity and ability to undergo degradation were studied.
- Homology-based model of porcine CYP1A1 was generated for the first time.
- Aa residues crucial for dioxin binding to the pCYP1A1 active site were identified.
- TCDD shown high affinity to pCYP1A1 and the greatest distance to its active site.
- Particular dioxins differ in their molecular interactions with pCYP1A1.

Polychlorinated dibenzo-p-dioxins (PCDDs) are widespread by-products of human industrial activity. They accumulate in tissues of animals and humans, exerting numerous adverse effects on different systems. In living organisms, dioxins are metabolized by enzymes of the cytochrome P450 family, including CYP1A1. Particular dioxin congeners differ in their toxicity level and ability to undergo biodegradation. Since the molecular mechanisms underlying dioxin susceptibility or resistance to biodegradation are unknown, in the present study the molecular interactions between five selected dioxins and porcine CYP1A1 protein were investigated. It was found that the ability of a dioxin to undergo CYP1A1-mediated degradation is associated mainly with the number and position of chlorine atoms in the dioxin molecule. Among all examined congeners, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) demonstrated the highest affinity to CYP1A1 and, at the same time, the greatest distance to the active site of the enzyme. Interestingly, in contrast to other dioxins, the binding of the TCDD molecule to the porcine CYP1A1 active site resulted in a rapid and continuous closure of substrate channels. All the information may help to explain the extended half-life of TCDD in living organisms as well as its high toxicity.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemosphere - Volume 168, February 2017, Pages 205-216
نویسندگان
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