Alnajar Seema, Khadka Bijendra, Gupta Radhey S
Department of Biochemistry and Biomedical Sciences, McMaster University, HamiltonON, Canada.
Front Microbiol. 2017 Jul 31;8:1409. doi: 10.3389/fmicb.2017.01409. eCollection 2017.
Bifidobacteria comprises an important group/order of bacteria whose members have widespread usage in the food and health industry due to their health-promoting activity in the human gastrointestinal tract. However, little is known about the underlying molecular properties that are responsible for the probiotic effects of these bacteria. The enzyme ribonucleotide reductase (RNR) plays a key role in all organisms by reducing nucleoside di- or tri- phosphates into corresponding deoxyribose derivatives required for DNA synthesis, and RNR homologs belonging to classes I and III are present in either most or all Comparative analyses of these RNR homologs have identified several novel sequence features in the forms of conserved signature indels (CSIs) that are exclusively found in bifidobacterial RNRs. Specifically, in the large subunit of the aerobic class Ib RNR, three CSIs have been identified that are uniquely found in the homologs. Similarly, the large subunit of the anaerobic class III RNR contains five CSIs that are also distinctive characteristics of bifidobacteria. Phylogenetic analyses indicate that these CSIs were introduced in a common ancestor of the and retained by all descendants, likely due to their conferring advantageous functional roles. The identified CSIs in the bifidobacterial RNR homologs provide useful tools for further exploration of the novel functional aspects of these important enzymes that are exclusive to these bacteria. We also report here the results of homology modeling studies, which indicate that most of the bifidobacteria-specific CSIs are located within the surface loops of the RNRs, and of these, a large 43 amino acid insert in the class III RNR homolog forms an extension of the allosteric regulatory site known to be essential for protein function. Preliminary docking studies suggest that this large CSI may be playing a role in enhancing the stability of the RNR dimer complex. The possible significances of the identified CSIs, as well as the distribution of RNR homologs in the , are discussed.
双歧杆菌是一类重要的细菌菌群，其成员因其在人类胃肠道中的健康促进活性而在食品和健康产业中广泛应用。然而，对于这些细菌产生益生菌效应的潜在分子特性，我们知之甚少。核糖核苷酸还原酶（RNR）在所有生物体中都起着关键作用，它将核苷二磷酸或三磷酸还原为DNA合成所需的相应脱氧核糖衍生物，并且大多数或所有双歧杆菌中都存在属于I类和III类的RNR同源物。对这些RNR同源物的比较分析已经确定了几个新的序列特征，这些特征以保守特征插入缺失（CSIs）的形式存在，并且仅在双歧杆菌的RNR中发现。具体而言，在需氧I b类RNR的大亚基中，已鉴定出三个CSIs，这些CSIs仅在该同源物中发现。同样，厌氧III类RNR的大亚基包含五个CSIs，这些也是双歧杆菌的独特特征。系统发育分析表明，这些CSIs是在双歧杆菌的共同祖先中引入的，并被所有后代保留，这可能是由于它们赋予了有利的功能作用。在双歧杆菌RNR同源物中鉴定出的CSIs为进一步探索这些重要酶在这些细菌中独有的新功能方面提供了有用的工具。我们在此还报告了同源建模研究的结果，这些结果表明，大多数双歧杆菌特异性CSIs位于RNR的表面环内，其中，III类RNR同源物中一个43个氨基酸的大插入形成了已知对蛋白质功能至关重要的变构调节位点的延伸。初步对接研究表明，这个大的CSI可能在增强RNR二聚体复合物的稳定性方面发挥作用。本文讨论了已鉴定的CSIs的可能意义，以及RNR同源物在双歧杆菌中的分布情况。
