PROPERTIES OF AORTIC LYSYL OXIDASE

赖氨酰氧化酶在弹性蛋白和胶原蛋白的成熟过程中起关键作用 通过将这些蛋白质中的肽基赖氨酸氧化成肽基而形成的结缔组织 交联剂的反应性前体--α-氨基-己二酸-伽马半醛 在这些蛋白质中。本课题拟从结构和催化两方面进行探索 为了更全面地了解这种酶的性质 该酶在正常和病理状态下的生物学功能 结缔组织。使用高度纯化的蛋白质，这是 在结缔组织中发现的多种形式的赖氨酰氧化酶将是 通过肽图谱、初级序列研究和与 针对每一种酶制备的特异性抗血清。酶的反应 原弹性蛋白，一种可溶的弹性蛋白，以及酶的能力 氧化原弹性蛋白和类似原弹性蛋白的合成肽将是 研究、评估这些多肽的凝聚作用和 原弹性蛋白对其底物电位的影响。有机化合物的化学性质 将研究酶的辅因子与羰基反应的可能性及其可能性 将对该酶的作用机制进行研究。 我们将进一步完善我们现有的完全合成的赖氨酸氧化酶检测方法。 为潜在的临床和实验用途而开发，并利用这种检测方法 探讨其活性部位的立体化学及其抑制机制 胺。赖氨酰氧化酶的细胞作用部位也将被研究。

Lysyl oxidase plays a critical role in the maturation of elastin and collagen of connective tissues by oxidizing peptidyl lysine in these proteins to peptidyl alpha-amino-adipic-gamma-semialdehyde, the reactive precursor to crosslinkages in these proteins. This project proposes to probe the structural and catalytic properties of this enzyme in order to more fully understand the important biological function of this enzyme in normal and pathological states of connective tissue. Using the highly purified protein, the basis of the multiplicity of forms of lysyl oxidase found in connective tissues will be explored by peptide mapping, primary sequence studies, and reactivity with specfic antisera prepared against each enzyme species. The reaction of enzyme with tropoelastin a soluble form of elastin, and the ability of enzyme to oxidize tropoelastin and synthetic peptides resembling tropoelastin will be investigated, assessing the affect of coacervation of these peptides and tropoelastin on their substrate potential. The chemical nature of an organic cofactor of the enzyme with carbonyl reactivity will be studied and its possible role in the mechanism of the enzyme will be investigated. We will further refine the totally synthetic assay for lysyl oxidase we have developed for potential clinical and experimental use and utilize this assay to probe the stereochemistry of the active site and mechanism of inhibition by amines. The cellular site of action of lysyl oxidase will also be investigated.