Chopping and Changing: the Evolution of the Flavin-dependent Monooxygenases.
Chopping and Changing: the Evolution of the Flavin-dependent Monooxygenases.
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DOI：
10.1016/j.jmb.2016.07.003
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发表时间：
2016-07-31
影响因子：
5.6
通讯作者：
Laskowski RA
中科院分区：
文献类型：
--
作者：
Mascotti ML;Juri Ayub M;Furnham N;Thornton JM;Laskowski RA
黄素依赖的单加氧酶发挥着多种重要的生理作用，也是非常强大的生物技术工具。根据它们的序列和生化特征，这些酶被分为八个不同的类别(A-H)。通过结合结构和序列分析以及系统发育推断，我们探索了A、B、E、F和G类的进化历史，并证明了它们的多结构域结构反映了它们的系统发育关系，表明它们分歧的主要进化步骤可能来自不同结构域的招募。此外，每个类别内的功能差异似乎是其他机制的结果，例如一组复杂的单点突变。我们的结果强化了这样的观点，即辅因子依赖的酶的进化的主要制约因素是辅因子的功能结合。此外，这个家族的一个显著特征是，在这里研究的所有类别中，关键的黄素腺嘌呤二核苷酸结合域的序列至少被分成两部分。我们提出了一组复杂的进化事件，这些事件导致了这个家族中不同类别的起源。结构域结构的变化反映了黄素单加氧酶的系统发育。不同领域的招聘一直是推动其演变的主要力量。黄素单加氧酶的一个显著特征是黄素腺嘌呤二核苷酸结合域是分裂的。通过结构变化，单加氧酶的种类从祖先的领域中出现。
Flavin-dependent monooxygenases play a variety of key physiological roles and are also very powerful biotechnological tools. These enzymes have been classified into eight different classes (A–H) based on their sequences and biochemical features. By combining structural and sequence analysis, and phylogenetic inference, we have explored the evolutionary history of classes A, B, E, F, and G and demonstrate that their multidomain architectures reflect their phylogenetic relationships, suggesting that the main evolutionary steps in their divergence are likely to have arisen from the recruitment of different domains. Additionally, the functional divergence within in each class appears to have been the result of other mechanisms such as a complex set of single-point mutations. Our results reinforce the idea that a main constraint on the evolution of cofactor-dependent enzymes is the functional binding of the cofactor. Additionally, a remarkable feature of this family is that the sequence of the key flavin adenine dinucleotide-binding domain is split into at least two parts in all classes studied here. We propose a complex set of evolutionary events that gave rise to the origin of the different classes within this family. Changes in domain architectures reflect the phylogeny of flavin monooxygenases. Recruitment of different domains has been the main force driving its evolution. A notable feature of flavin monooxygenases is that the flavin adenine dinucleotide-binding domain is split. Classes of monooxygenases emerged from an ancestral domain by structural changes.