STAFF PRIORITY TIME FE K & CU K XAS STUDIES OF CYTOCHROME OXIDASE & MODELS

员工优先时间 FE K

• 批准号: 6658728
• 负责人: BRITT HEDMAN
• 金额: $ 14.32万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6658728
• 关键词: biological products; biomaterials; biomedical resource; proteins; spectrometry; structural biology; technology /technique

Cytochrome oxidase (CcO) is known to possess four metal centers - two heme and two Cu sites. The catalytic center of CcO is defined by the two metal sites, heme a3 and CuB, which are associated to form a binuclear center. Numerous studies have propose that the two metal centers be closely spaced and bridged, but the identity of the bridging ligand in the "as-isolated" enzyme remains unresolved. Work at Harvard has given rise to several binuclear synthetic complexes which are viable analogs of the CcO site. They include a bridged Fe(III)-O-Cu(II) complex which reproduces the most prominent electronic features of the oxidized CcO site, and a CN- bridged analog which has potential relevance to cyanide toxicity. These analogues present a significant challenge for EXAFS analysis because: i) from the Fe viewpoint the octaethylporphrin ligand is rigid and contributes significant multiple scattering (MS) terms to the overall EXAFS signal, ii) a mono bridge, such as O2- will contribute strong MS as the bridge angle approaches linearity and be a significant contributor from either the Cu or the Fe EXAFS viewpoint, and iii) multinuclear bridges, such as CN- could have very complicated 4-body MS interactions (again angularly dependent). We intend to perform complete MS XAS analysis on these models and enzymes.

已知细胞色素氧化酶 (CcO) 拥有四个金属中心 - 两个血红素和两个铜位点。 CcO 的催化中心定义为 两个金属位点，血红素 a3 和 CuB，结合形成 双核中心。 大量研究表明这两种金属 中心间隔很近并且桥接，但是 “分离的”酶中的桥配体仍未解决。 工作 哈佛大学已经产生了几种双核合成配合物 它们是 CcO 位点的可行类似物。 它们包括桥接 Fe(III)-O-Cu(II) 复合物再现了最突出的 氧化 CcO 位点的电子特征以及 CN 桥接的类似物 这与氰化物毒性有潜在的相关性。 这些类似物 对 EXAFS 分析提出了重大挑战，因为： i) 从Fe的观点来看，八乙基卟啉配体是刚性的并且有助于 整体 EXAFS 的显着多重散射 (MS) 项 信号，ii) 单桥，例如 O2- 将贡献强大的 MS，如 桥角接近线性并且是一个重要的贡献者 从 Cu 或 Fe EXAFS 角度来看，以及 iii) 多核 桥，例如 CN- 可能有非常复杂的 4 体 MS 相互作用（同样是角度相关的）。 我们打算执行 对这些模型和酶进行完整的 MS XAS 分析。