A bioinformatics analysis of 3400 lytic polysaccharide oxidases from family AA9
A bioinformatics analysis of 3400 lytic polysaccharide oxidases from family AA9
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DOI：
10.1016/j.carres.2017.04.012
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发表时间：
2017-08-07
影响因子：
3.1
通讯作者：
Henrissat, Bernard
中科院分区：
文献类型：
--
作者：
Lenfant, Nicolas;Hainaut, Matthieu;Henrissat, Bernard
AA 9家族的裂解性多糖单加氧酶催化纤维素和相关多糖中糖苷键的氧化裂解。AA 9 LPMO的N-末端一半显示出巨大的序列变异性，这与迄今为止观察到的这些酶的底物简单性相矛盾。为了了解在家庭中普遍存在的高多原性的原因，我们已经进行了聚类分析的N-末端区域的3400序列的家庭AA 9 LPMO，并已评估的一致性的集群与远端可见的功能，可能伴随着功能的差异。设计了一种基于局部成对比对的方法，以避免全局多重比对的缺陷。我们的分析允许定义64个簇，其成功地分离了与LPMO家族AA 9相关的几个可见特征，例如存在碳水化合物结合模块、未知功能的模块以及在保持催化铜的组氨酸支架的第一个残基处的明显H -> R取代。我们的分析表明，AA 9序列的N-末端一半的超变不是由随机进化驱动的，因为序列相似性并不完全遵循分类学。结果表明，一些集群可能能够靶向甲壳素，而不是纤维素，和C1或C4氧化（或缺乏）的偏好，似乎并不构成一个强大的进化约束。从进化的角度来看，除了组氨酸支架的保守性之外，N-末端的一半序列似乎没有什么限制。适用于AA 9 LPMO的N-末端一半的弱进化限制解释了它们的超变性和多原性。(C)2017爱思唯尔有限公司版权所有。
Lytic polysaccharide monooxygenases of family AA9 catalyze the oxidative cleavage of glycosidic bonds in cellulose and related polysaccharides. The N-terminal half of AA9 LPMOs displays a huge sequence variability that is in contradiction with the substrate simplicity so far observed for these enzymes. To understand the cause of the high multigenicity that prevails in the family, we have performed a clustering analysis of the N-terminal region of 3400 sequences of family AA9 LPMOs, and have evaluated the coincidence of the clusters with distal visible features that may accompany functional differences. A method based on local pairwise alignments was devised to avoid the pitfalls of a global multiple alignment. Our analysis allowed the definition of 64 clusters, which successfully segregated several visible features associated to LPMO family AA9, such as the presence of carbohydrate-binding modules, of modules of unknown function and of the conspicuous H -> R substitution at the first residue of the histidine brace that holds the catalytic copper. Our analysis shows that the hypervariability of the N-terminal half of the AA9 sequences is not driven by random evolution as sequence similarity does not follow solely taxonomy. The results suggest that some clusters are perhaps able to target chitin instead of cellulose, and that preference for C1 or C4 oxidation (or lack thereof), does not appear to constitute a strong evolutionary constraint. On an evolutionary standpoint, there seems to be little constraints that apply to the N-terminal half of the sequences other than the conservation of the histidine brace. The weak evolutionary constraints that apply to the N-terminal half of AA9 LPMOs explain both their hypervariability and multigenicity. (C) 2017 Elsevier Ltd. All rights reserved.