The human "magnesome": detecting magnesium binding sites on human proteins.
The human "magnesome": detecting magnesium binding sites on human proteins.
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DOI：
10.1186/1471-2105-13-s14-s10
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发表时间：
2012
影响因子：
3
通讯作者：
Casadio R
中科院分区：
文献类型：
--
作者：
Piovesan D;Profiti G;Martelli PL;Casadio R
由于镁离子在几个重要的生物过程和相关的分子发病机制中的相关性，镁在分子医学中的研究正在增加。从蛋白质的共价结构中仍然很难预测人链是否参与镁结合。这主要是由于在蛋白质和蛋白质复合物的镁结合位点的结构特征的信息很少。镁的结合特征，不同于其他二价阳离子如钙和锌的结合特征，是难以捉摸的。在这里，我们解决一个问题，是相关的蛋白质注释：有多少人的蛋白质可以结合Mg 2+？我们的分析是利用最近实施的博洛尼亚注释资源（BAR-PLUS）进行的，BAR-PLUS是一种非层次聚类方法，它依赖于来自30多万个物种的约1400万个蛋白质的成对序列比较，并将其分组为簇，在统计验证后可以安全地继承注释。在对最新版本的人类蛋白质组进行聚类分配之后，我们可以分配推定的Mg结合位点的人类蛋白质的总数为3，751。在这些蛋白质中，2，688个直接从人类模板继承注释，1，063个从其他生物体的模板继承注释。蛋白质结构在给定的簇内是高度保守的。在将给定序列与用基于隐马尔可夫模型（HMM）的程序获得的包含给定簇的蛋白质结构进行比对之后，结构性质的转移是可能的。有趣的是，一组370个人序列从模板继承Mg 2+结合位点，与模板共享小于30%的序列同一性。我们描述并提供了“人类magnesome”，一组人类蛋白质组的蛋白质，继承了镁离子的假定结合。使用我们的BAR-hMG，包括对应于387个序列的1，341个镁结合蛋白结构的251个簇足以将3，751个人类序列中的约13，689个残基注释为“镁结合”。因此，蛋白质结构充当用于人类序列的结构和功能注释的三维种子。该数据库专门收集了所有可以根据我们的程序注释为“镁结合”的人类蛋白质、相应的结构和BAR+簇（它们从中获得注释）（http：//bar.biocomp.unibo.it/mg）。
Magnesium research is increasing in molecular medicine due to the relevance of this ion in several important biological processes and associated molecular pathogeneses. It is still difficult to predict from the protein covalent structure whether a human chain is or not involved in magnesium binding. This is mainly due to little information on the structural characteristics of magnesium binding sites in proteins and protein complexes. Magnesium binding features, differently from those of other divalent cations such as calcium and zinc, are elusive. Here we address a question that is relevant in protein annotation: how many human proteins can bind Mg2+? Our analysis is performed taking advantage of the recently implemented Bologna Annotation Resource (BAR-PLUS), a non hierarchical clustering method that relies on the pair wise sequence comparison of about 14 millions proteins from over 300.000 species and their grouping into clusters where annotation can safely be inherited after statistical validation. After cluster assignment of the latest version of the human proteome, the total number of human proteins for which we can assign putative Mg binding sites is 3,751. Among these proteins, 2,688 inherit annotation directly from human templates and 1,063 inherit annotation from templates of other organisms. Protein structures are highly conserved inside a given cluster. Transfer of structural properties is possible after alignment of a given sequence with the protein structures that characterise a given cluster as obtained with a Hidden Markov Model (HMM) based procedure. Interestingly a set of 370 human sequences inherit Mg2+ binding sites from templates sharing less than 30% sequence identity with the template. We describe and deliver the "human magnesome", a set of proteins of the human proteome that inherit putative binding of magnesium ions. With our BAR-hMG, 251 clusters including 1,341 magnesium binding protein structures corresponding to 387 sequences are sufficient to annotate some 13,689 residues in 3,751 human sequences as "magnesium binding". Protein structures act therefore as three dimensional seeds for structural and functional annotation of human sequences. The data base collects specifically all the human proteins that can be annotated according to our procedure as "magnesium binding", the corresponding structures and BAR+ clusters from where they derive the annotation (http://bar.biocomp.unibo.it/mg).