Synthetic Analogues of Cysteinate-Ligated Metalloenzymes

半胱氨酸连接金属酶的合成类似物

• 批准号: 6949969
• 负责人: PRISCILLA LUGO-MAS
• 金额: $ 3.18万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949969
• 关键词: amides; chemical models; chemical synthesis; cysteine; enzyme activity; enzyme mechanism; enzyme substrate analog; iron sulfur protein; metalloenzyme; nuclear magnetic resonance spectroscopy; predoctoral investigator; superoxides

DESCRIPTION (provided by applicant): Nitrile hydratase (NHase) and superoxide reductase (SOR) are a new class of non-heme iron enzymes that contain cysteinate sulfurs coordinated to iron. Their function varies enormously from nitrile hydration, with NHases, to superoxide reduction, with SOR. Although the structures of NHase and SOR have been defined, a number of unresolved questions concerning the mechanisms of action of both enzymes have yet to be adequately addressed. To this regard, the research described in this proposal will focus on modeling the reactivity of NHase in an effort to understand the mechanism of nitrile hydrolysis as well as the role that peptide amides and cysteinate sulfur ligand(s) might play in promoting function; determining whether the oxygenated sulfurs are necessary for NHase activity, or whether they are simply an artifact; understanding and determining how the electronic and reactivity properties of Pel 11-peroxides containing only nitrogen donors are affected by the incorporation of a thiolate sulfur and make direct comparisons between structurally related model systems that differ by only one ligand. To achieve these goals, different synthetic model complexes will be synthesized and their reactivity studied.

描述（由申请人提供）：腈水合酶（NHase）和超氧化物还原酶（SOR）是一类新的非血红素铁酶，含有与铁配位的半胱氨酸硫。它们的功能变化很大，从腈水合，与NHases，超氧化物还原，与SOR。虽然已经确定了NHase和SOR的结构，但关于这两种酶的作用机制的一些未解决的问题尚未得到充分解决。在这方面，本提案中描述的研究将侧重于模拟腈水解酶的反应性，以了解腈水解的机制以及肽酰胺和半胱氨酸硫配体在促进功能中可能发挥的作用;确定氧化硫是否是腈水解酶活性所必需的，或者它们是否只是人工产物;理解和确定如何通过硫醇盐硫的掺入影响仅含氮供体的Pel 11-过氧化物的电子和反应性性质，并在结构上相关的模型系统之间进行直接比较，这些模型系统仅相差一个配体。为了实现这些目标，将合成不同的合成模型配合物，并研究它们的反应性。