Heme enzyme structure and function.
Heme enzyme structure and function.
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DOI：
10.1021/cr400415k
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发表时间：
2014-04-09
期刊：
影响因子：
62.1
通讯作者：
Poulos, Thomas L.
中科院分区：
文献类型：
--
作者：
Poulos, Thomas L.
金属卟啉在整个生物圈中被广泛使用，其中血红素（铁原卟啉IX，图1）是最丰富且使用最广泛的之一。血红素在蛋白质之间穿梭电子，就像线粒体呼吸一样，或者像球蛋白一样运输和储存O 2。在Mason（1）和Hayaishi（2）发现O2 O原子可以通过酶促作用结合到有机底物中（这代表了加氧酶的开创性发现）之后，血红素在更活跃的酶促化学转化中的作用开始受到重视。虽然这些研究中使用的酶不含血红素，但不久之后含血红素的加氧酶也被发现。1958年，Klingenberg（3）和Garfinkel（4）在微粒体中发现了一种不寻常的色素，当在CO存在下还原时，产生了一个峰在450 nm的光谱，而不是预期的420 nm峰。于是，P450这个名字就诞生了。1964年，大村和佐藤（5，6）表明，这种“色素”实际上是一种蛋白质，这种奇怪的血红素蛋白的功能在Estabrook等人的开创性研究中变得清晰。(7)这证明了450 nm色素参与类固醇羟基化。因此，到20世纪60年代中期，人们确定血红素通过某种方式催化有机底物的羟基化在生物学中起着积极的作用。虽然这些发现无疑标志着研究血红素加氧酶的现代方法的开始，但血红素的酶作用可以追溯到1903年辣根过氧化物酶（HRP）被描述的时候。(8)事实上，由于各种中间体易于纯化和稳定，HRP主导了血红素酶的研究，直到P450被发现。
Metalloporphyrins are widely used throughout the biosphere, and of these heme (iron protoporphyrin IX, Figure 1) is one of the most abundant and widely used. Heme shuttles electrons between proteins as in mitochondrial respiration or transports and stores O 2 as with the globins. The role of heme in more active enzymatic chemical transformations began to be appreciated just after the discovery by Mason (1) and Hayaishi (2) that O 2 O atoms can be enzymatically incorporated into organic substrates which represented the seminal discovery of oxygenases. While the enzymes used in these studies did not contain heme, it was not too long before heme-containing oxygenases also were discovered. In 1958 Klingenberg (3) and Garfinkel (4) found an unusual pigment in microsomes that when reduced in the presence of CO generated a spectrum with a peak at 450 nm instead of the expected 420 nm peak. Hence the name P450 was born. In 1964 Omura and Sato (5, 6) showed that this “pigment” is actually a protein and the function of this strange heme protein became clear in a seminal study by Estabrook et al.(7) that demonstrated the involvement of the 450 nm pigment in steroid hydroxylation. Thus by the mid-1960s it was established that heme plays an active role in biology by somehow catalyzing the hydroxylation of organic substrates. While these discoveries certainly mark the beginning of modern approaches to studying heme enzyme oxygenases, the enzymatic role of heme dates much earlier to 1903 when horseradish peroxidase (HRP) was described.(8) Indeed, owing to the ease of purification and stability of the various intermediates, HRP dominated heme enzyme studies until P450 was discovered.
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DOI：
10.1073/pnas.74.8.3203
发表时间：
1977-01-01
影响因子：
11.1
作者：
ARNOLD, WP;MITTAL, CK;MURAD, F
通讯作者：
MURAD, F
DOI：
10.1073/pnas.72.12.4854
发表时间：
1975-01-01
影响因子：
11.1
作者：
ADMAN, E;WATENPAUGH, KD;JENSEN, LH
通讯作者：
JENSEN, LH
影响因子：
2.9
作者：
Bonagura, CA;Sundaramoorthy, M;Poulos, TL
通讯作者：
Poulos, TL
影响因子：
2.9
作者：
Blodig, W;Doyle, WA;Piontek, K
通讯作者：
Piontek, K
影响因子：
15
作者：
BORDWELL, FG;CHENG, JP;ZHANG, XM
通讯作者：
ZHANG, XM