Binding site-based classification of coronaviral papain-like proteases
Binding site-based classification of coronaviral papain-like proteases
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DOI：
10.1002/prot.20802
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发表时间：
2006-02-15
影响因子：
2.9
通讯作者：
Ménard, R
中科院分区：
文献类型：
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作者：
Sulea, T;Lindner, HA;Ménard, R
冠状病毒复制酶基因编码一个或两个木瓜蛋白酶样酶(称为PL1Pro和PL2Pro)，参与复制酶多蛋白的N端加工，从而有助于形成介导基因组复制的病毒复制酶复合体。利用3D-JURAY元预测因子的共识折叠识别，然后建模和改进，我们开发了一个存在于严重急性呼吸综合征冠状病毒(SCOV)基因组中的单个PLPro的结构模型，该模型基于与Hausp催化核心域的显著结构关系，Hausp是一种泛素特异性蛋白酶(USP)。通过结合SCOV PLPRO模型和比较序列分析，我们发现所有已知的冠状病毒PLPRO根据其结合位点的结构可以分为两类。一组包括所有PL2pros和一些PL1pros，其特征是具有限制性的USP样结合位点。这个基团被称为R-基团。来自一些冠状病毒的其余PL1pros形成另一组，具有更开放的木瓜酶样结合位点，被称为O-组。这种基于两组结合位点的分类与迄今积累的实验数据一致，表明PLPro介导的多蛋白处理和PLPro抑制的特异性。它还对PLPro介导的裂解位点的基于相似性的注释进行了独立的评估，并提供了与以前基于系统发育分析的分组进行比较的基础。
The coronavirus replicase gene encodes one or two papain-like proteases (termed PL1pro and PL2pro) implicated in the N-terminal processing of the replicase polyprotein and thus contributing to the formation of the viral replicase complex that mediates genome replication. Using consensus fold recognition with the 3D-JURY meta-predictor followed by model building and refinement, we developed a structural model for the single PLpro present in the severe acute respiratory syndrome coronavirus (SCoV) genome, based on significant structural relationships to the catalytic core domain of HAUSP, a ubiquitin-specific protease (USP). By combining the SCoV PLpro model with comparative sequence analyses we show that all currently known coronaviral PLpros can be classified into two groups according to their binding site architectures. One group includes all PL2pros and some of the PL1pros, which are characterized by a restricted USP-like binding site. This group is designated the R-group. The remaining PL1pros from some of the coronaviruses form the other group, featuring a more open papain-like binding site, and is referred to as the O-group. This two-group, binding site-based classification is consistent with experimental data accumulated to date for the specificity of PLpro-mediated polyprotein processing and PLpro inhibition. It also provides an independent evaluation of the similarity-based annotation of PLpro-mediated cleavage sites, as well as a basis for comparison with previous groupings based on phylogenetic analyses.