MOLECULAR INTERACTION OF ISOALLOXAZINE DERIVATIVES.
MOLECULAR INTERACTION OF ISOALLOXAZINE DERIVATIVES.
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异恶嗪衍生物的分子相互作用。
DOI：
10.1073/pnas.45.12.1708
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发表时间：
1958
影响因子：
11.1
通讯作者：
Robert M. Amick
中科院分区：
文献类型：
--
作者：
H. A. Harbury;Kathryn F. LaNoue;Paul A. Loach;Robert M. Amick
Theorell和Kuhn以及他们的同事1-5已经提出了相当多的证据I-L支持这样的观点，即黄素单核苷酸(FMN)的磷酸基团在FMN与“老黄酶”的蛋白质成分的结合中起着重要作用，似乎在其他FMN-蛋白质系统中也有类似的情况。有人认为，在生理pH值的“老黄色酶”中，带负电荷的磷酸基团与蛋白质的带正电荷的氨基结合。4‘5不太清楚的是蛋白质与FMN的异四氧嘧啶部分之间相互作用的性质。从游离FMN和蛋白质结合的FMN在吸收光谱、荧光光谱和氧化还原电位上的不同可以明显看出这种相互作用的发生。此外，在“老黄酶”的蛋白质组分中加入核黄素会导致酶活性的发展和核黄素荧光的猝灭。3.Kuhn和他的同事们的早期研究结果(广泛回顾6-9)中，对核黄素类似物及其衍生物的维生素活性和当添加到“老黄酶”的蛋白质中时引起酶活性的能力进行了检验，这是在许多实验室进行的广泛的抗代谢研究，6-9和最近Theorell和Nygaard4‘5的动力学数据都与FMN的异四氧嘧啶部分在蛋白质-FMN相互作用中起关键作用的观点一致。这种相互作用可能不仅在一种FMN蛋白和另一种FMN蛋白之间，而且在可逆的相互转化状态和单一黄素蛋白的化合物之间也是不同的。这可能在更大程度上适用于更复杂的黄素腺嘌呤二核苷酸蛋白和金属黄素蛋白。以类似于本实验室正在进行的对血红素蛋白、辣根过氧化物酶的系统研究的方式来检查黄素蛋白系统的关联功能似乎是有意义的。1然而，尽管关于金属卟啉与非蛋白质配体相互作用的大量信息的可获得性促进了对血红素蛋白的研究，但对于异四氧嘧啶衍生物，几乎没有类似的信息。在目前的交流中，我们报告了为更详细的研究做准备而进行的定向准备的研究。
Theorell and Kuhn and their co-workers1-5 have presented considerable evidence i-l support of the view that the phosphate group of flavin mononucleotide (FMN) plays an important role in the binding of FMN to the protein component of the "old yellow enzyme," and it seems likely that a similar situation obtains in other FMN-protein systems. It has been suggested that, in the "old yellow enzyme" at physiological values of pH, the negatively charged phosphate group is bound to positively charged amino groups of the protein.4' 5 Less clear is the nature of the interaction between protein and the isoalloxazine portion of FMN. That such interaction occurs is evident from the fact that free FMN and protein-bound FMN differ in absorption spectrum, fluorescence spectrum, and oxidation-reduction potential. Moreover, addition of riboflavin to the protein component of the "old yellow enzyme" leads both to the development of enzymic activity and to quenching of the fluorescence of riboflavin.3 4 The results of the early investigations by Kuhn and his colleagues (reviewed extensively6-9), in which riboflavin analogues and derivatives were examined both for vitamin activity and for ability to give rise to enzymic activity when added to the protein of the "old yellow enzyme," the extensive antimetabolite studies performed in many laboratories,6-9 and the recent kinetic data of Theorell and Nygaard4'5 are all consistent with the idea that the isoalloxazine part of FMN plays a key role in protein-FMN interaction. Such interaction may be expected to differ not only between one FMN-protein and another, but also between reversibly interconvertible states and compounds of a single flavoprotein. This may hold to an even greater extent for the more complex flavin adenine dinucleotide-proteins and metalloflavoproteins. It would seem of interest to examine the linked functions10 of flavoprotein systems in a manner analogous to the systematic study of the heme protein, horseradish peroxidase, now in progress in this laboratory.1 However, whereas studies of heme proteins are facilitated by the availability of considerable information on the interaction of metalloporphyrins with nonprotein ligands,'2 little analogous information exists for isoalloxazine derivatives. In the present communication we report on studies undertaken for purposes of orientation preparatory to more detailed investigations.