Catalytic turnover dependent modification of the Pseudomonas aeruginosa heme oxygenase (pa-HO) by 5,6-O-isopropyledine-2-O-allyl-ascorbic acid.
Catalytic turnover dependent modification of the Pseudomonas aeruginosa heme oxygenase (pa-HO) by 5,6-O-isopropyledine-2-O-allyl-ascorbic acid.
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5,6-O-异丙啶-2-O-烯丙基-抗坏血酸对铜绿假单胞菌血红素加氧酶 (pa-HO) 的催化转换依赖性修饰。
DOI：
10.1016/j.jinorgbio.2007.08.007
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发表时间：
2008
影响因子：
3.9
通讯作者：
Wilks,Angela
中科院分区：
文献类型：
--
作者：
Bhakta,MehulN;Olabisi,Ayodele;Wimalasena,Kandatege;Wilks,Angela
血红素加氧酶（HO）催化血红素通过NADPH依赖性转化为胆绿素，并通过三个连续的氧化步骤释放铁和CO。血红素的氧化在替代还原剂，如抗坏血酸的存在下，已被广泛用于表征HO中的氧活化的机制，而不改变反应的化学性质。NADPH依赖性细胞色素P450还原酶（CPR）和抗坏血酸介导的反应在机理上非常相似，因为两者都使用分子氧来引发反应。在本手稿中，我们报告的抗坏血酸衍生物，5，6-O-异丙基-2-O-烯丙基-抗坏血酸，在催化分区之间的反应血红素胆绿素的转换，和一个替代的途径，陷阱的verdoheme中间体作为蛋白质修饰的结果。我们建议，以下激活的5，6-O-异丙基-2-O-烯丙基-抗坏血酸的阳离子自由基，蛋白质修饰的结果通过烷基化的活性位点亲核试剂（天冬氨酸或谷氨酸），捕获的FeIII-verdoheme中间体。潜在的网站的修改和相关的机制FeIII-verdoheme转换胆绿素进行了讨论。
Heme oxygenase (HO) catalyzes the NADPH dependent conversion of heme to biliverdin with the release of iron and CO via three successive oxygenation steps. The oxidation of heme in the presence of alternate reductants, such as ascorbic acid, has been used extensively to characterize the mechanism of oxygen activation in HO without altering the chemistry of the reaction. NADPH-dependent cytochrome P450 reductase (CPR) and ascorbic acid mediated reactions are mechanistically very similar, in that both use molecular oxygen to initiate the reaction. In the present manuscript, we report on an ascorbic acid derivative, 5,6-O-isopropyledine-2-O-allyl-ascorbic acid, that during catalysis partitions the reaction between the conversion of heme to biliverdin, and an alternate pathway that traps the verdoheme intermediate as a result of protein modification. We propose that following activation of 5,6-O-isopropyledine-2-O-allyl-ascorbic acid to the cation radical, protein modification results via alkylation of an active site nucleophile (Asp or Glu), trapping the FeIII-verdoheme intermediate. The potential site of the modification and the relevance to the mechanism of FeIII-verdoheme conversion to biliverdin is discussed.