协调和pseudo-cooperativity谷胱甘肽S-transferase恶性疟原虫。
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Liebau E, F·德·玛丽亚,Burmeister C, Perbandt M, Turella P, Antonini G, Federici G, Giansanti F, Stella L, Lo贝洛M, Caccuri,里奇G
协调和pseudo-cooperativity谷胱甘肽S-transferase恶性疟原虫。
生物化学杂志。2005年7月15日;280 (28):26121 - 8。2005年5月11日Epub。
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15888443 (在PubMed]
- 文摘
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绑定和催化性质的谷胱甘肽S-transferase恶性疟原虫(PfGST)研究了通过荧光,稳态和动态实验研究状态,对接模拟。这种酶显示一个独特的可逆的低亲和力过渡,没有观察到在其他消费税,涉及G-site和变化明显的K (D)对谷胱甘肽(GSH)从200年到0.18毫米,过渡到高亲和力构象触发的同步绑定两个谷胱甘肽分子二聚的酶,它表现为一个未修正的正合行为,称为“pseudo-cooperativity。”The high affinity enzyme is able to activate GSH, lowering its pK(a) value from 9.0 to 7.0, a behavior similar to that found in all known GSTs. Using 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, this enzyme reveals a potential optimized mechanism for the GSH conjugation but a low catalytic efficiency mainly due to a very low affinity for this co-substrate. Conversely, PfGST efficiently binds one molecule of hemin/monomer. The binding is highly cooperative (n(H) = 1.8) and occurs only when GSH is bound to the enzyme. The thiolate of GSH plays a crucial role in the intersubunit communication because no cooperativity is observed when S-methylglutathione replaces GSH. Docking simulations suggest that hemin binds to a pocket leaning into both the G-site and the H-site. The iron is coordinated by the amidic nitrogen of Asn-115, and the two carboxylate groups are in electrostatic interaction with the epsilon-amino group of Lys-15. Kinetic and structural data suggest that PfGST evolved by optimizing its binding property with the parasitotoxic hemin rather than its catalytic efficiency toward toxic electrophilic compounds.