PROPERTIES OF AORTIC LYSYL OXIDASE

赖氨酰氧化酶在弹性蛋白和胶原蛋白的成熟中起着关键作用， 通过将这些蛋白质中的肽基赖氨酸氧化成肽基 α-氨基-己二酸-γ-半醛，交联的反应前体 在这些蛋白质。 本项目旨在探索结构和催化 这种酶的性质，以便更充分地了解重要的 这种酶在正常和病理状态下的生物学功能 结缔组织 利用高度纯化的蛋白质， 在结缔组织中发现的赖氨酰氧化酶的多种形式将是 通过肽图谱、一级序列研究和与 针对每种酶制备的特异性抗血清。 酶的反应 弹性蛋白原是弹性蛋白的可溶形式，酶能够 氧化弹性蛋白原和类似弹性蛋白原的合成肽将被 研究，评估这些肽的凝聚作用， 原弹性蛋白对它们的底物电位的影响。 有机物的化学性质 将研究具有羰基反应性的酶的辅因子，并研究其可能的 将研究酶的作用机制。 我们将进一步完善赖氨酰氧化酶的全合成测定法， 开发用于潜在的临床和实验用途，并利用该测定来 探讨活性部位的立体化学和抑制机理， 胺。 赖氨酰氧化酶的细胞作用部位也将进行研究。

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.