IMIDAZOLINE BINDING DOMAIN ON MAO-B

描述：（摘自摘要）各种咪唑啉和胍 衍生物在外周组织中引起不同的细胞反应， 在中枢神经系统中，通常很难归因于已知的 受体信号系统 这样的分子还表现出高亲和力， 膜蛋白（咪唑啉结合位点）， 已知激素的受体，并识别内源性生物活性 模拟这些化合物的某些作用的物质。 这些 观察结果表明了以前未表征的细胞信号系统。 然而，咪唑啉结合位点的功能仍未得到解决。 出乎意料和特别重要的是，最近的数据表明， 咪唑啉结合蛋白的成员与A和B相同 单胺氧化酶（MAO）的亚型，催化儿茶酚胺的酶 神经递质和异生物质。 MAO上的咪唑啉结合结构域是 不同于识别基于 抑制剂如帕吉林和丙炔苯丙胺， 所有组织。 MAO-B上咪唑啉结构域的有限可及性 是这个应用程序的重点。 具体目标：1。 确定单胺氧化酶的结构域 与咪唑啉-胍鎓配体相互作用。 2. 确定是否 是组织中MAO-B的结构差异， 其咪唑啉结合结构域的差异可及性。 3. 确定 如果Mao B上咪唑啉结合位点的表观不可及性 某些组织涉及与细胞特异性辅助蛋白的相互作用 或内源性掩蔽物质。 MAO是某些情绪障碍管理中的治疗靶点， 帕金森病的早期阶段和酶活性可能有助于 其他神经退行性疾病的发病。 一些示威者 人的咪唑啉结合蛋白实际上是单胺氧化酶 同工型表明，单胺氧化酶接受多种调节输入， 在各种疾病状态的病因学和/或管理中具有重要意义。 从拟议的研究中产生的信息可能涉及一种新的 对这种酶的调节方法。

DESCRIPTION: (Taken from the Abstract) Various imidazoline and guanidinium derivatives elicit diverse cellular responses in both peripheral tissues and in the central nervous system that are often difficult to attribute to known receptor signalling systems. Such molecules also exhibit high affinity for membrane proteins (imidazoline binding sites) that are distinct from receptors for known hormones and recognize an endogenous bioactive substance(s) that mimics some of the effects of these compounds. These observations suggest a previously uncharacterized cell signalling system. However, the functionality of imidazoline binding sites remains unresolved. Unexpectedly and of particular significance, recent data indicate that two members of imidazoline binding proteins are identical to the A and B isoforms of monoamine oxidase (MAO), enzymes that catalyze catecholamine neurotransmitters and xenobiotics. The imidazoline binding domain on MAO is distinct from the enzyme active site that recognizes the mechanism based inhibitors such as pargyline and deprenyl and is not equally accessible in all tissues. The limited accessibility of the imidazoline domain on MAO-B is the focus of this application. Specific Aims: 1. Identify the structural domains of monoamine oxidase interacting with imidazoline-guanidinium ligands. 2. Determine if there are structural differences in MAO-B in tissues where the enzyme exhibits differential accessibility of its imidazoline binding domain. 3. Determine if the apparent inaccessibility of the imidazoline binding site on Mao B in certain tissues involves interaction with cell specific accessory proteins or an endogenous masking substance. MAO is a therapeutic target in the management of certain mood disorders, the early phases of Parkinson's Disease and enzyme activity may contribute to the onset of other neurodegenerative disorders. The demonstration that some types of imidazoline binding proteins in humans are indeed monoamine oxidase isoforms suggests that MAO receives multiple regulatory inputs that may be of significance in the etiology and/or management of various disease states. Information generated from the proposed studies may implicate a novel approach to the regulation of this enzyme.