Living with Oxygen.
Living with Oxygen.
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DOI：
10.1021/acs.accounts.8b00245
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发表时间：
2018-08-21
影响因子：
18.3
通讯作者：
Winkler JR
中科院分区：
文献类型：
--
作者：
Gray HB;Winkler JR
50 多年前，哥本哈根就开始研究金属-氧配合物的电子结构。这项工作导致了这样的预测：四方多键过渡金属-氧代在元素周期表中的铁-钌-锇氧代壁之外将不稳定，并且三键金属-氧代不能被质子化，即使在最强的布朗斯台德酸中也是如此。在这个理论中，只有双键金属-氧可以吸引质子，碱度是辅助配体的电子供给能力的函数。近年来，电子结构与反应性的这种相关性变得越来越重要，最值得注意的是，人们普遍认识到高价铁氧是对地球生命至关重要的生物反应的中间体。在这篇文章中，我们将注意力集中在细胞色素 P450 对惰性有机底物的氧化作用上，因为这些反应涉及多重键合的铁-氧。我们强调，P450 铁氧代是强氧化剂，如果底物不快速氧化，它们会破坏附近的氨基酸；我们认为，这些高价铁氧是非常危险的活性氧，大自然肯定找到了使它们失效的方法。更深入地研究这个问题，主要是通过检查蛋白质数据库中的数千个结构，我们发现 P450 和其他需要氧气才能发挥作用的酶具有从活性位点区域延伸到蛋白质表面的酪氨酸和色氨酸链。酪氨酸位于细菌 P450 的血红素活性位点附近，而色氨酸则位于大多数人类酶中最接近的位置。从空穴跳跃图中获取的高价铁-氧存活时间范围从几纳秒到毫秒，具体取决于最近的色氨酸或酪氨酸残基与血红素的距离。在我们提出的机制中，通过 Tyr/Trp 链的多步空穴隧道（跳跃）将破坏性氧化空穴引导至蛋白质表面，在那里它可以被可溶性蛋白质或小分子还原剂淬灭。据信，地球的含氧大气层是在大约 25 亿年前形成的，自最后一个普遍进化祖先以来，酪氨酸和色氨酸出现频率的增加可能部分是为了应对环境毒素 O2 而发展的酶保护功能的结果。
Work on the electronic structures of metal–oxo complexes began in Copenhagen over 50 years ago. This work led to the prediction that tetragonal multiply bonded transition metal–oxos would not be stable beyond the iron–ruthenium–osmium oxo wall in the periodic table and that triply bonded metal–oxos could not be protonated, even in the strongest Brønsted acids. In this theory, only double bonded metal–oxos could attract protons, with basicities being a function of the electron donating ability of ancillary ligands. Such correlations of electronic structure with reactivity have gained importance in recent years, most notably owing to the widespread recognition that high-valent iron–oxos are intermediates in biological reactions critical to life on Earth. In this Account, we focus attention on the oxygenations of inert organic substrates by cytochromes P450, as these reactions involve multiply bonded iron–oxos. We emphasize that P450 iron–oxos are strong oxidants, so strong that they would destroy nearby amino acids if substrates are not oxygenated rapidly; it is our view that these high-valent iron–oxos are such dangerous reactive oxygen species that Nature surely found ways to disable them. Looking more deeply into this matter, mainly by examining many thousands of structures in the Protein Data Bank, we have found that P450s and other enzymes that require oxygen for function have chains of tyrosines and tryptophans that extend from active-site regions to protein surfaces. Tyrosines are near the heme active sites in bacterial P450s, whereas tryptophan is closest in most human enzymes. High-valent iron–oxo survival times taken from hole hopping maps range from a few nanoseconds to milliseconds, depending on the distance of the closest Trp or Tyr residue to the heme. In our proposed mechanism, multistep hole tunneling (hopping) through Tyr/Trp chains guides the damaging oxidizing hole to the protein surface, where it can be quenched by soluble protein or small molecule reductants. As the Earth’s oxygenic atmosphere is believed to have developed about 2.5 billion years ago, the increase in occurrence frequency of tyrosine and tryptophan since the last universal evolutionary ancestor may be in part a consequence of enzyme protective functions that developed to cope with the environmental toxin, O2.
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DOI：
10.1073/pnas.0905020106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Costentin, Cyrille;Robert, Marc;Teillout, Anne-Lucie
通讯作者：
Teillout, Anne-Lucie
影响因子：
4.6
作者：
GRAY, HB;HARE, CR
通讯作者：
HARE, CR
DOI：
10.1002/cbic.201600176
发表时间：
2016-08-03
期刊：
Chembiochem : a European journal of chemical biology
影响因子：
--
作者：
Holtmann D;Hollmann F
通讯作者：
Hollmann F
影响因子：
10.7
作者：
Brooks, DJ;Fresco, JR;Singh, M
通讯作者：
Singh, M
DOI：
10.1073/pnas.1012381107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Ener, Maraia E.;Lee, Young-Tae;Cheruzel, Lionel
通讯作者：
Cheruzel, Lionel