MODEL STUDIES OF HYDROPORPHYRIN-CONTAINING ENZYMES

含氢卟啉酶的模型研究

• 批准号: 3284030
• 负责人: ALAN M STOLZENBERG
• 金额: $ 11.2万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3284030
• 关键词: chemical structure function; cofactor; enzyme mechanism; enzyme model; enzyme structure; ligands; methane; nitrites; porphyrin structure; stereochemistry; sulfite reductase; tetrapyrroles; vitamin B12 compound

The objective of this research program is to develop an understanding of the structural, electronic, and mechanistic features of hydroporphyrin-containing enzymes. These catalyze important steps in key metabolic processes including the inorganic carbon, nitrogen, and sulfur cycles and many of the main energy producing pathways of microorganisms. The program has three specific aims: (1) to determine the significant differences in the properties of the complexes of hydroporphyrins, porphyrins, and other tetrapyrroles, (2) to synthesize and characterize a structural model of the linked siroheme-Fe4S4 active site of nitrite and sulfite reductases, and (3) to develop a reactivity model for the F430 dependent reductive cleavage of S-methyl coenzyme M to methane. Synthetic, small molecule analogues of enzyme active sites and prosthetic groups will be used in these investigations. The first aim will be addressed by testing the hypotheses that porphyrin, hydroporphyrins, corrins, and other tetrapyrroles are distinguished by the optimal hole size and range of hole sizes readily accessible in their complexes and that the substituent stereochemistry can modulate the range of readily accessible hole sizes. The hypotheses will be tested by examining chemical changes that require large changes in metal ion radius. Ligand binding/spin state equilibria of Ni(II) tetrapyrroles and the correlation between the accessibility of the Ni(I) oxidation state and the saturation level and substituent stereochemistry of the hydroporphyrin macrocycle will be investigated, among others. The third aim will be achieved by exploring the reactions of NiI(OEiBC)-, the only reported Ni(I) tetrapyrrole except for F430. The mechanism(s) of the reactions will be determined. Alkyl- Ni(OEiBC) complexes will be synthesized and evaluated as potential reaction intermediates.

该研究计划的目标是开发一种 对结构、电子和机械的理解 含氢卟啉酶的特征。 这些催化 关键代谢过程中的重要步骤，包括无机代谢 碳、氮、硫循环以及许多主要能源 微生物的生产途径。 该计划有三个 具体目标：（1）确定显着差异 氢卟啉、卟啉和络合物的性质 其他四吡咯，(2) 合成并表征 连接的西罗血红素-Fe4S4 活性位点的结构模型 亚硝酸盐和亚硫酸盐还原酶，以及 (3) 产生反应性 S-甲基的 F430 依赖性还原裂解模型 辅酶M转化为甲烷。 合成的小分子类似物 酶活性位点和辅基将用于这些 调查。 第一个目标将通过测试来解决 假设卟啉、氢卟啉、corrins 和其他 四吡咯的特点是最佳孔径和范围 在其复合体中容易接近的孔尺寸，并且 取代基立体化学可以轻松调节范围 可触及的孔尺寸。 这些假设将通过检查来检验 需要金属离子半径发生较大变化的化学变化。 四吡咯 Ni(II) 的配体结合/自旋态平衡和 Ni(I) 氧化态可达性之间的相关性 以及饱和度和取代基立体化学 除其他外，还将研究氢卟啉大环。 第三个目标将通过探索反应来实现 NiI(OEiBC)-，除 F430 外唯一报道的 Ni(I) 四吡咯。 将确定反应的机制。 烷基- Ni(OEiBC) 配合物将被合成并评估为 潜在的反应中间体。