Structural and thermochemical characterization of lipoxygenase-catechol complexes.
Structural and thermochemical characterization of lipoxygenase-catechol complexes.
复制标题
脂氧合酶-儿茶酚复合物的结构和热化学表征。
DOI：
10.1021/bi981989t
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发表时间：
1998
期刊：
影响因子：
2.9
通讯作者：
FunkJr,MO
中科院分区：
文献类型：
--
作者：
Pham,C;Jankun,J;Skrzypczak-Jankun,E;Flowers2nd,RA;FunkJr,MO
用等温滴定量热法检测了天然大豆铁（II）脂氧化酶3和4-硝基儿茶酚（一种已知的酶抑制剂）之间的配合物，并用x射线晶体学对其进行了表征。这种化合物在蛋白质的中心腔中靠近基本的铁原子，但没有与铁原子成键。相对于它们在天然酶中的位置，铁配体在形成复合物时经历了显著的重排；在复合物中，一个水分子与铁分子结合，一个组氨酸配体离开铁分子，与儿茶酚发生氢键反应。这些位置的变化导致配合物中铁的三角金字塔配位几何。分子模型和力场计算预测4-硝基儿茶酚与脂氧合酶3中心腔之间存在不止一种稳定的配合物，但与晶体结构中发现的小分子具有相同取向的相互作用是最有利的。这些观察结果揭示了脂氧合酶与小分子之间相互作用的具体细节，并提出了铁原子配体环境变化可能是产物活化反应或催化机制的一个特征的可能性。
A complex between native, iron(II) soybean lipoxygenase 3 and 4-nitrocatechol, a known inhibitor of the enzyme, has been detected by isothermal titration calorimetry and characterized by X-ray crystallography. The compound moors in the central cavity of the protein close to the essential iron atom, but not in a bonding arrangement with it. The iron ligands experience a significant rearrangement upon formation of the complex relative to their positions in the native enzyme; a water molecule becomes bound to iron in the complex, and one histidine ligand moves away from the iron to become involved in a hydrogen bonding interaction with the catechol. These changes in position result in a trigonal pyramid coordination geometry for iron in the complex. Molecular modeling and force field calculations predict more than one stable complex between 4-nitrocatechol and the central cavity of lipoxygenase 3, but the interaction having the small molecule in the same orientation as the one found in the crystal structure was the most favorable. These observations reveal specific details of the interaction between lipoxygenase and a small molecule and raise the possibility that changes in the ligand environment of the iron atom could be a feature of the product activation reaction or the catalytic mechanism.