MODELS FOR CYTOCHROME P-450 HYDROXYLASES

细胞色素 P-450 羟化酶模型

• 批准号: 2020927
• 负责人: JAMES P COLLMAN
• 金额: $ 38.26万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2020927
• 关键词: Mossbauer spectrometry; Raman spectrometry; X ray crystallography; aminoacid analog; chemical models; chemical structure function; chemical synthesis; cysteine; cytochrome P450; electrochemistry; electron probe spectrometry; enzyme mechanism; enzyme model; enzyme substrate analog; flavins; heme; hemoprotein structure; hydroxylation; infrared spectrometry; metalloenzyme; molecular site; nuclear magnetic resonance spectroscopy; oxygenases; porphyrins; ruthenium; unspecific monooxygenase

This research is directed towards functional analogues of the enzyme family cytochromes P-450. These mixed-function oxygenases are involved in sterol biosynthesis and metabolism, in drug detoxification, and in bioactivation of xenobiotics to toxic and carcinogenic products. The present studies are intended to provide a molecular background for the mechanisms of oxygen activation and transfer, and of suicide inhibition during the function of the enzymes P-450. Novel metalloporphyrin compounds will by synthesized and examined as catalysts for the oxygenation of various organic substrates. Analogues of ,he intermediate stages in the P-450 reaction cycle will be isolated, characterized, and then reaction chemistry will be studied. This work will focus on the special role of the cysteine mercaptide ligand and of activators in the heterolytic reductive cleavage of dioxygen during the P-450 reaction cycle. Various electrochemical techniques with flavin mediators will be used to mimic the two critical single-electron transfer steps in the P-450 reaction sequence. Electrochemistry, kinetics measurements, synthetic organic and inorganic chemistry and a range of spectroscopic techniques (1H NMR, IR, Raman, MCD, Mossbauer, X-ray diffraction and EXAFS) will be used in this molecular biomimetic research. Ruthenium analogues of the iron atoms in heme centers will be prepared and studied in the context of P-450 chemistry.

这项研究是针对功能类似物的

项目成果

Inhibition of electrocatalytic O(2) reduction of functional CcO models by competitive, non-competitive, and mixed inhibitors.

通过竞争性、非竞争性和混合抑制剂抑制功能性 CcO 模型的电催化 O(2) 还原。

• DOI: 10.1021/ic900825y
• 发表时间: 2009
• 期刊: Inorganic chemistry
• 影响因子: 4.6
• 作者: Collman,JamesP;Dey,Abhishek;Barile,ChristopherJ;Ghosh,Somdatta;Decreau,RichardA
• 通讯作者: Decreau,RichardA

Catalytic reduction of O2 by cytochrome C using a synthetic model of cytochrome C oxidase.

• DOI: 10.1021/ja9001579
• 发表时间: 2009-04-15
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Collman JP;Ghosh S;Dey A;Decréau RA;Yang Y
• 通讯作者: Yang Y

Water-soluble polymer-bound biomimetic analogues of cytochrome C oxidase catalyze 4e- reduction of O2 to water.

细胞色素 C 氧化酶的水溶性聚合物结合仿生类似物催化 O2 4e-还原成水。

• DOI: 10.1021/ic034140w
• 发表时间: 2003
• 期刊: Inorganic chemistry.
• 作者: Collman,JamesP;Fudickar,Werner;Shiryaeva,Irina
• 通讯作者: Shiryaeva,Irina