STEREOCONTROL IN SOYBEAN LOX-1

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 多不饱和脂肪酸被脂氧合酶（LOX）家族的双加氧酶氧化。 非血红素铁负责高度立体选择性地从脂肪酸中提取初始氢，随后非束缚氧与自由基结合。 大豆LOX-1（Soybean LOX-1，SBL 1）是目前研究最多的脂肪氧合酶催化模型。 这些研究得到了高分辨率X射线晶体结构的支持。SBL 1帮助建立了许多脂肪氧合酶催化的基本概念，特别是这些是反应的高特异性和手性产物的形成;例如从花生四烯酸中产生5S-氢过氧化物。 产品的性质导致的假设的基板能够采取一个相反的方向结合在脂氧合酶的活性位点。这一假说是开放的辩论，由于缺乏与绑定基板的LOX结构。最近的一项研究表明，SBL1的第一次氧化的头优先基板方向。在没有结合底物的X-射线结构的情况下，建模是理解通过分析脂氧合酶反应的立体化学而开发的概念的有用方法。由于LOX结合自旋标记的脂肪酸，因此可以直接测量doxylstearic acid（DSA）和氮氧自由基自旋标记之间的距离以建立底物结合模式。 Dr. Gaffney制定了开展此类研究的计划，ACERT已通过提供距离测量对后续服务请求做出回应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Polyunsaturated fatty acids are oxygenated by the dioxygenases of lipoxygenase (LOX) family of enzymes. Nonheme iron is responsible for highly stereoselective initial hydrogen abstraction from the fatty acid and subsequently non-tethered oxygen binds to the radical. Soybean LOX-1 (SBL1) is the best-studied model of lipoxygenase catalysis. The studies are supported by the availability of high resolution x-ray crystal structures. SBL1 helped to establish many fundamental concepts of lipoxygenase catalysis, in particular these are the high specificity of the reaction and formation of a chiral product; e.g. 5S-hydroperoxide from arachidonic acid. The nature of products led to a hypothesis of the substrate being capable of adopting a reversed orientation of binding in the lipoxygenase active site. This hypothesis is open to debate due to lack of LOX structure with bound substrate. A recent study suggested a head-first substrate orientation for the first oxygenation by SBL1. In the absence of the X-ray structure with bound substrate, modeling was a useful approach to understanding concepts developed by analysis of the stereochemistry of the lipoxygenase reaction. Since LOX binds spin-labeled fatty acids it is possible to directly measure distances between doxylstearic acid (DSA) and nitroxide spin label to establish the mode of substrate binding. Dr. Gaffney nursed the plan to carry out such study, ACERT has responded to subsequent service request by providing distance measurements.