Functionally unrelated signalling proteins contain a fold similar to Mg2+-dependent endonucleases
Functionally unrelated signalling proteins contain a fold similar to Mg2+-dependent endonucleases
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DOI：
10.1016/s0968-0004(00)01582-6
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发表时间：
2000-06-01
影响因子：
13.8
通讯作者：
Dlakic, M
中科院分区：
文献类型：
--
作者：
Dlakic, M
273最终增加Cdc2磷酸化12。其次，尽管可能性较小，但CdtB也可能具有核酸内切酶活性，从而导致DNA损伤，从而触发复制检查点系统并使Cdc2失活（参考文献13）。考虑到图1中五种未表征的蛋白质（以及其他许多已确定的蛋白质）属于致病菌，我们可以推测，一些病原体已经发展出了侵袭宿主的机制，其中包括可能改变细胞周期或磷脂信号的内切酶或磷酸酶。一般来说，不同蛋白质之间的结构同源性提出了一个问题，即它们是从不同的祖先聚合成一个相似的折叠，还是从同一祖先分化成功能不同的蛋白质。基于这里提出的结果，我认为存在一个具有古老磷酸酯酶折叠的大型金属酶超家族，它作为在所有三个生命王国中发生的功能多样化蛋白质的支架。由于具有共同的催化机制，这些酶的核心在所有成员中得以保留。另一方面，对各种底物的识别，从核酸到磷脂，可能还有蛋白质，有助于在连接核心链和螺旋的环中引入相当大的变化2,3。
273 ultimately increases Cdc2 phosphorylation12. Second, although less likely, CdtB could also have an endonuclease activity, therefore causing DNA damage that would trigger the replication checkpoint system and also inactivate Cdc2 (Ref. 13). Given the fact that five uncharacterized proteins in Fig. 1 (and many others in the complete set of identified proteins) belong to pathogenic bacteria, one can speculate that some pathogens have developed mechanisms for the host invasion that include putative endonucleases or phosphatases altering the cell cycle or phospholipid signalling. In general, structural homology between diverse proteins raises the question whether they converged to a similar fold from different ancestors or diverged into functionally distinct proteins from the same ancestor. Based on the results presented here, I argue for the existence of a large metalloenzyme superfamily with an ancient phosphoesterase fold, which served as a scaffold for functionally diverse proteins occurring in all three kingdoms of life. The core of these enzymes was preserved among all members because of a common catalytic mechanism. On the other hand, the recognition of various substrates, ranging from nucleic acids to phospholipids and possibly proteins, was instrumental in introducing considerable variations in the loops connecting core strands and helices2, 3.