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首页> 外文期刊>Biochemistry >Structural basis of phospholipase a(2) inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic Acid from a 1.7 a crystal structure(,).
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Structural basis of phospholipase a(2) inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic Acid from a 1.7 a crystal structure(,).

机译：植物生物碱马兜铃酸从1.7 a晶体结构合成磷脂酶a（2）抑制前列腺素合成的结构基础。

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This is the first structural observation of a plant product showing high affinity for phospholipase A(2) and regulating the synthesis of arachidonic acid, an intermediate in the production of prostaglandins. The crystal structure of a complex formed between Vipera russelli phospholipase A(2) and a plant alkaloid aristolochic acid has been determined and refined to 1.7 A resolution. The structure contains two crystallographically independent molecules of phospholipase A(2) in the form of an asymmetric dimer with one molecule of aristolochic acid bound to one of them specifically. The most significant differences introduced by asymmetric molecular association in the structures of two molecules pertain to the conformations of their calcium binding loops, beta-wings, and the C-terminal regions. These differences are associated with a unique conformational behavior of Trp(31). Trp(31) is located at the entrance of the characteristic hydrophobic channel which works as a passage to the active site residues in the enzyme. In the case of molecule A, Trp(31) is found at the interface of two molecules and it forms a number of hydrophobic interactions with the residues of molecule B. Consequently, it is pulled outwardly, leaving the mouth of the hydrophobic channel wide open. On the other hand, Trp(31) in molecule B is exposed to the surface and moves inwardly due to the polar environment on the molecular surface, thus narrowing the opening of the hydrophobic channel. As a result, the aristolochic acid is bound to molecule A only while the binding site of molecule B is empty. It is noteworthy that the most critical interactions in the binding of aristolochic acid are provided by its OH group which forms two hydrogen bonds, one each with His(48) and Asp(49).
机译：这是植物产品的首次结构观察，显示对磷脂酶A（2）具有高亲和力并调节花生四烯酸的合成，花生四烯酸是生产前列腺素的中间体。已确定Vi蛇罗氏磷脂酶A（2）与植物生物碱马兜铃酸之间形成的复合物的晶体结构，并将其提纯至1.7 A分辨率。该结构包含两个不对称二聚体形式的磷脂酶A（2）的晶体学独立分子，其中一个马兜铃酸分子与两个分子中的一个具体结合。在两个分子的结构中，由不对称分子缔合引入的最显着差异涉及其钙结合环，β翼和C端区域的构象。这些差异与Trp（31）的独特构象行为有关。 Trp（31）位于特征性疏水通道的入口，该通道作为通向酶中活性位点残基的通道。在分子A的情况下，在两个分子的界面处发现Trp（31），它与分子B的残基形成许多疏水相互作用。因此，它被向外拉，使疏水通道的嘴张开。另一方面，由于分子表面上的极性环境，分子B中的Trp（31）暴露于表面并向内移动，从而使疏水通道的开口变窄。结果，马兜铃酸仅在分子B的结合位点为空时才与分子A结合。值得注意的是，马兜铃酸的结合中最关键的相互作用是由其羟基形成的，该羟基形成两个氢键，每个氢键分别与His（48）和Asp（49）相连。

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