嗜热菌Lanuginosa脂肪酶与酶反应物复合物的晶体结构

Q4 Pharmacology, Toxicology and Pharmaceutics
A. McPherson, S. Larson, Andrew Kalasky
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引用次数: 4

摘要

了解真菌脂肪酶的作用细节及其界面活化机制。真菌脂肪酶对生物技术至关重要,它在脂水界面起作用,在那里它经历了一个鲜为人知的界面激活。影响其激活和抑制的生化因素也知之甚少。该研究为其活性和界面活化机理提供了依据。测定不同结晶形式的真菌脂肪酶及其酶促反应物和抑制剂的结构。x射线晶体学。在1.3 ~ 1.45 Å分辨率下,以三种空间群H32、P21和I222的晶体形式显示了热脂酶。菱形晶体有一个分子,缺少第241到252节段,作为不对称单元,分子组织为两个三聚体。单斜晶的不对称单元是6个完整的分子,组成两个几乎相同的三聚体,每个都表现出anNCS三轴。“盖子”螺旋始终关闭。寡聚成三聚体产生一个内部疏水腔,催化发生。在单斜晶和正交晶中,活性丝氨酸被酯化成脂肪酸。脂肪酶在它们的三聚疏水腔内结合了脂肪酸链长度约为18个碳的1,3-二酰基甘油。结果表明三聚体可能是酶在脂-水界面的活性形式。三聚体的形成可以解释“界面活化”。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Crystal Structures of Thermomyces (Humicola) Lanuginosa Lipase in Complex with Enzymatic Reactants
To understand the details of the action of fungal lipase and the mechanism for its observed interfacial activation. Fungal lipase, crucial to biotechnology, functions at the lipid - water interface where it undergoes a poorly understood interfacial activation. Biochemical factors influencing its activation and inhibition are also poorly understood. This study provides a basis for its activity and a plausible mechanism for interfacial activation. To determine the structures of fungal lipase in different crystal forms in complex with their enzymatic reactants and inhibitors. X-ray crystallography. Thermomyces lanuginosa lipase was visualized in three crystal forms, of space groups H32, P21 and I222 at 1.3 to 1.45 Å resolution. Rhombohedral crystals have one molecule, lacking segment 241 to 252, as an asymmetric unit, with molecules organized as two trimers. Monoclinic crystals’ asymmetric unit is six intact molecules organized as two, nearly identical trimers, each exhibiting an NCS threefold axis. The “lid” helix was consistently closed. Oligomerization into trimers creates an internal hydrophobic cavity where catalysis occurs. In monoclinic and orthorhombic crystals, active site serines were esterified to fatty acids. Lipase had bound within their trimeric, hydrophobic cavities 1,3-diacylglycerols with fatty acid chain lengths of about 18 carbons. Results suggest trimers are likely the active form of the enzyme at the lipid-water interface. Formation of trimers may provide an explanation for “interfacial activation”.
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来源期刊
Current Enzyme Inhibition
Current Enzyme Inhibition Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
1.30
自引率
0.00%
发文量
30
期刊介绍: Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
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