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Molecular mechanism of heme degradation catalyzed by heme oxygenase

血红素加氧酶催化血红素降解的分子机制

基本信息

批准号：
08044240
负责人：
YOSHIDA Tadashi
金额：
$ 7.17万
依托单位：
YAMAGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044240/
关键词：
Heme oxygenase Oxygenase O_2 activation mechanism Heme Degradation of heme CO Bieiverdin Bilirubin 酵素活性化機構ビリベリジンビリルビン

项目摘要

(1) We observed the resonance Raman spectra for alpha-hydroxyheme and verdoheme complexes of heme oxygensae (HO). We found that the ferric alpha-hydroxyheme and ferrous verdoheme complexes showed atypical Raman patterns, which are interpreted. as the result of the symmnetry lowering of the porphyrin-conjugating pi-electron system.(2) previously we found that histidine residue of HO was the proximal lignd of heme. To identify the axial heme lignd of HO-2, we prepared His45 to Ala (H45A) and His152 to Ala (H152A) mutants. H45A could form a 1 : 1 complex with hemin but was completely devoid of the heme degradation activity. A 5-coordinate-type ferrous NO EPR spectrum was observed for the heme-H45A complex. On the contrary, H152A mutant exhibited spectroscopic and enzymatic properties identical to those of wild-type. His132 of HO-1, Which corresponds to His152 of HO-2, was also not important for the heme degradation activity.(3) The O_2 and CO reactions with the heme, alpha-hydroxyheme, and veroheme complexes of HO were studied. The heme complexs of HO-1 and HO-2 have similar O_2 and CO binding properties. The O_2 affinities for heme and hydroxyheme・are very high, but the CO affinities are only 1-6-fold higher than the O_2 affinities. Thus, HO discriminate much more strongly against CO binding than myoglobin. The CO affinities of the verdoheme complex are about 10,000 times weaker than those of the heme complex. The positive charge on the verdoporphyrin ring causes a large decrease in reactivity of the iron.

(1)本文观察了血红素氧合物（HO）的α-羟基血红素和绿血红素复合物的共振拉曼光谱。我们发现，铁α-羟基血红素和亚铁绿血红素复合物显示非典型的拉曼模式，这是解释。这是卟啉共轭π电子系统对称性降低的结果。(2)我们以前发现HO的组氨酸残基是血红素的近端。为了鉴定HO-2的轴向血红素配体，我们制备了His 45至Ala（H45 A）和His 152至Ala（H152 A）突变体。H45 A能与血红素形成1：1的复合物，但完全没有血红素降解活性。血红素-H45 A复合物的EPR谱为5配位型亚铁NO。相反，H152 A突变体表现出与野生型相同的光谱和酶性质。HO-1的His 132（对应于HO-2的His 152）对血红素降解活性也不重要。(3)研究了HO的血红素、α-羟基血红素和异血红素配合物与O_2和CO的反应。HO-1和HO-2的血红素复合物具有相似的O_2和CO结合特性。血红素和羟基血红素·的O_2亲和力很高，而CO亲和力仅为O_2亲和力的1-6倍。因此，HO比肌红蛋白更强烈地歧视CO结合。绿血红素复合物的CO亲和力比血红素复合物的CO亲和力弱约10，000倍。绿卟啉环上的正电荷导致铁的反应性大幅降低。