Biological Systems Discovery In Silico: Radical S-Adenosylmethionine Protein Families and Their Target Peptides for Posttranslational Modification
Biological Systems Discovery In Silico: Radical S-Adenosylmethionine Protein Families and Their Target Peptides for Posttranslational Modification
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DOI：
10.1128/jb.00040-11
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发表时间：
2011-06-01
影响因子：
3.2
通讯作者：
Basu, Malay Kumar
中科院分区：
文献类型：
--
作者：
Haft, Daniel H.;Basu, Malay Kumar
生物信息学和比较基因组学中的数据挖掘方法通常依赖于先前计算中蛋白质家族的工作定义。相比之下，部分系统发育分析 (PPP) 在搜索在同一生物系统中发挥不同作用的共存蛋白质家族时优化了家族大小。在对极其多样化的自由基 S-腺苷甲硫氨酸 (SAM) 酶超家族的大规模研究中，PPP 帮助建立了 68 个 TIGRFAM 隐马尔可夫模型 (HMM) 的集合，这些模型定义了不重叠且功能不同的亚家族。许多人将自由基 SAM 酶视为多组分生物系统的分子标记；还构建了定义其伙伴蛋白的 HMM。新发现的系统包括五组蛋白质家族，其中至少一个标记是自由基 SAM 酶，而另一个标记由相邻基因编码，是一种短肽，预计将成为其翻译后修饰的底物。最普遍的，在超过 125 个基因组中，具有我们指定为 SCIFF（45 个残基中的 6 个半胱氨酸）的肽，在梭菌纲中是保守的，这种分布与假定的细菌素活性不一致。第二个新系统的特点是一对串联的假定肽修饰自由基 SAM 酶，与高度分化的肽家族相关，其中唯一明显保守的特征是一系列 His-Xaa-Ser 重复序列。第三个系统将自由基 SAM 结构域肽成熟酶与含硒代半胱氨酸的靶标配对，表明硒具有新的生物学作用。这些以及与预测的目标肽共存的其他几种新型成熟酶与 PqqE、枯草溶菌素 A 成熟酶 AlbA、预测的分枝菌素和 Nif11 类肽成熟酶以及厌氧硫酸酯酶和醌血红蛋白胺脱氢酶的激活剂共享 C 端额外的 4Fe4S 结合结构域。 TIGR04085 检测到，具有此附加结构域的自由基 SAM 酶的数量显着超过参考基因组中组合的羊毛硫抗生素合酶和环脱水酶，同时高度富集了表面目标为小肽的成员。比较基因组学证据的解释表明来自其中几个系统的天然产物具有意想不到的（非细菌素）作用。
Data mining methods in bioinformatics and comparative genomics commonly rely on working definitions of protein families from prior computation. Partial phylogenetic profiling (PPP), by contrast, optimizes family sizes during its searches for the cooccurring protein families that serve different roles in the same biological system. In a large-scale investigation of the incredibly diverse radical S-adenosylmethionine (SAM) enzyme superfamily, PPP aided in building a collection of 68 TIGRFAMs hidden Markov models (HMMs) that define nonoverlapping and functionally distinct subfamilies. Many identify radical SAM enzymes as molecular markers for multicomponent biological systems; HMMs defining their partner proteins also were constructed. Newly found systems include five groupings of protein families in which at least one marker is a radical SAM enzyme while another, encoded by an adjacent gene, is a short peptide predicted to be its substrate for posttranslational modification. The most prevalent, in over 125 genomes, featuring a peptide that we designate SCIFF (six cysteines in forty-five residues), is conserved throughout the class Clostridia, a distribution inconsistent with putative bacteriocin activity. A second novel system features a tandem pair of putative peptide-modifying radical SAM enzymes associated with a highly divergent family of peptides in which the only clearly conserved feature is a run of His-Xaa-Ser repeats. A third system pairs a radical SAM domain peptide maturase with selenocysteine-containing targets, suggesting a new biological role for selenium. These and several additional novel maturases that cooccur with predicted target peptides share a C-terminal additional 4Fe4S-binding domain with PqqE, the subtilosin A maturase AlbA, and the predicted mycofactocin and Nif11-class peptide maturases as well as with activators of anaerobic sulfatases and quinohemoprotein amine dehydrogenases. Radical SAM enzymes with this additional domain, as detected by TIGR04085, significantly outnumber lantibiotic synthases and cyclodehydratases combined in reference genomes while being highly enriched for members whose apparent targets are small peptides. Interpretation of comparative genomics evidence suggests unexpected (nonbacteriocin) roles for natural products from several of these systems.