BIOLOGICAL VANADIUM--MODELS OF STRUCTURE/FUNCTION

生物钒——结构/功能模型

• 批准号: 2704555
• 负责人: VINCENT L PECORARO
• 金额: $ 15.41万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2704555
• 关键词: X ray spectrometry; acid phosphatase; bromine; chlorine; electron nuclear double resonance spectroscopy; electron spin resonance spectroscopy; enzyme activity; enzyme mechanism; enzyme model; halogenation; hydrogen peroxide; mass spectrometry; metalloenzyme; model design /development; nuclear magnetic resonance spectroscopy; oxidation; peroxidases; vanadium

DESCRIPTION: (adapted from applicant's abstract) Vanadium was once considered an oddity in biology with ill defined structures and even more obscure functions. In the past two decades, scientists have realized that this element is found in marine enzymes that may be responsible for many useful natural products and ultimately may serve as a new therapeutic regiment for oral treatment of diabetes. During our previous three years of funding, we have focused on preparing functional models for the vanadium haloperoxidases. Early last year, we presented the most efficient haloperoxidase reactivity model compounds yet reported. Unlike previous models, our compounds are functional as mononuclear, monoperoxo species, exactly as proposed for VHPOs. About six months ago, we made a major breakthrough in that we can oxidize chloride at a measurable rate. We estimate that our reaction is at least 10 (and more likely 100 fold) faster than any previous vanadium based chloride oxidation catalyst. We also now have data that may address the functional role of amavadin which we have suggested may be a rudimentary bromo- or iodoperoxidase. The studies proposed for the next funding period build on these major advances. 1) Probe the mechanism of vanadium haloperoxidases by establishing the factors that lead to activation of our bromide and chloride oxidation catalysts. As necessary, we will develop and characterize new ligand sets that serve as more efficient agents in these reactions. 2) Expand our studies of the reaction of V(IV) species with hydrogen peroxide since these may be important interaction that define the reactivity of amavadin and the cellular metabolism of vanadium insulin mimics. 3) Through collaboration with several spectroscopists, develop new methodologies that will allow scientists to define to higher chemical resolution V=O binding sites in proteins. Since V=O substitutes for many divalent ions, this approach can be broadly applied to a variety of metalloproteins. We propose that high molecular weight acid phosphatases can convert to VHPOs in the presence of vanadate.

描述：（改编自申请人的摘要）Vanessa曾经是 被认为是生物学中的一种奇怪现象， 更多模糊功能 在过去的二十年里，科学家们 意识到这种元素存在于海洋酶中， 负责许多有用的天然产物，并最终可能服务于 作为口服治疗糖尿病的新治疗方案。 期间 我们过去三年的资金，我们专注于准备 钒卤代过氧化物酶的功能模型。 去年年初， 我们提出了最有效的卤过氧化物酶反应模型 化合物的报道。 与以前的模型不同，我们的化合物 功能与单核、单过氧物质相同，完全符合 VHPO。 大约六个月前，我们取得了重大突破， 能以可测量的速率氧化氯化物。 我们估计， 反应至少比任何反应快10倍（更可能是100倍）。 以前的钒基氯化物氧化催化剂。 我们现在也有 数据可能解决amavadin的功能作用，我们有 可能是一种基本的溴或碘过氧化物酶。 研究 在这些重大进展的基础上，为下一个供资期提出了一些建议。 第一章 通过建立钒卤代过氧化物酶的分子生物学模型探讨钒卤代过氧化物酶的作用机制 导致溴化物和氯化物氧化活化的因素 催化剂的 如有必要，我们将开发和表征新的配体 在这些反应中充当更有效的试剂的集合。 2)扩大 我们研究了V（IV）物种与过氧化氢的反应， 因为这些可能是重要相互作用， amavadin和钒胰岛素模拟物的细胞代谢。 第三章 通过与多位光谱学家合作，开发新的 科学家们可以用这种方法来定义更高的化学物质 解析蛋白质中的V=O结合位点。 由于V=O， 许多二价离子，这种方法可以广泛应用于各种 金属蛋白 我们提出高分子量酸性磷酸酶可以转化为 在钒酸盐存在下的VHPO。