Spectroscopic features of cytochrome P450 reaction intermediates.

Spectroscopic features of cytochrome P450 reaction intermediates.
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DOI:
10.1016/j.abb.2010.12.008
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发表时间:
2011-03-01
影响因子:
3.9
通讯作者:
Sligar SG
Sligar SG
中科院分区:
生物学3区
文献类型:
--
作者:
Luthra A;Denisov IG;Sligar SG

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细胞色素P450是血红素单加氧酶的一个大类,具有11,500多种同工酶,已在所有生物界的生物体中鉴定。这些酶负责催化数十种化学氧化转化,如羟基化、环氧化、N-脱甲基等,具有非常广泛的底物范围。历史上,这些酶的名称来自“色素450”,这是由于还原CO饱和态的UV-Vis吸收光谱中Soret带的不寻常位置。尽管许多同工酶的详细的生化表征,以及后来发现的其他'P450-like血红素酶',如一氧化氮合酶和氯过氧化物酶,现象学术语'细胞色素P450'仍然是常用的指示功能活性蛋白质的基本光谱特征,这是现在已知的是由于存在的巯基配体的血红素铁。具有咪唑配体(如肌红蛋白和血红蛋白)的血红素蛋白以及P450的非活性形式的特征在于在420 nm处的Soret最大值。这一历史观点突出了光谱方法在一般生化研究中的重要性,特别是对于血红素酶,其中血红素铁和卟啉大环的存在提供了丰富多样的特定光谱标记物,可用于监测催化循环的活性中间体之间的化学转化和过渡。
Cytochromes P450 constitute a broad class of heme monooxygenase enzymes with more than 11,500 isozymes which have been identified in organisms from all biological kingdoms. These enzymes are responsible for catalyzing dozens chemical oxidative transformations such as hydroxylation, epoxidation, N-demethylation, etc., with very broad range of substrates. Historically these enzymes received their name from ‘pigment 450’ due to the unusual position of the Soret band in UV-Vis absorption spectra of the reduced CO-saturated state. Despite detailed biochemical characterization of many isozymes, as well as later discoveries of other ‘P450-like heme enzymes’ such as nitric oxide synthase and chloroperoxidase, the phenomenological term ‘cytochrome P450’ is still commonly used as indicating an essential spectroscopic feature of the functionally active protein which is now known to be due to the presence of a thiolate ligand to the heme iron. Heme proteins with an imidazole ligand such as myoglobin and hemoglobin as well as an inactive form of P450 are characterized by Soret maxima at 420 nm. This historical perspective highlights the importance of spectroscopic methods for biochemical studies in general, and especially for heme enzymes, where the presence of the heme iron and porphyrin macrocycle provides rich variety of specific spectroscopic markers available for monitoring chemical transformations and transitions between active intermediates of catalytic cycle.
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