The modular structure of alpha/beta-hydrolases: similarity of the N- and C-terminal domains to other proteins

To analyse the structural similarities of the N- and C-terminal domains, representative protein structures of each oxyanion hole type from the proteins of alpha/beta-hydrolase superfamilies 8 to 12 were selected from the Lipase Engineering Database (<a href="https://led.biocatnet.de/">https://led.biocatnet.de/</a>). The structures of the N- and C-terminal domains and the core domains were extracted and saved in separate .pdb files, which were then used to compare the domains by the "all against all" structure comparison tool on the Dali webserver (<a href="http://ekhidna2.biocenter.helsinki.fi/dali/">http://ekhidna2.biocenter.helsinki.fi/dali/</a>). In a second step, the PDB (Protein Data Bank) search tool on the Dali server was used to compare the N- and C-terminal domains against all structures in PDB25, a subset resulting from clustering the whole PDB database with an identity threshold of 25%. The Dali server has different measures to determine similarity between proteins. The Z-Score is a measure for structural similarity, where a Z-score >2 implies significant structural similarities and thus a similar fold. Besides the Z-Score, the output also contains information about the root-mean-square deviation (rmsd) and the sequence identity.

为探究N端与C端结构域的结构相似性，本研究从脂肪酶工程数据库（Lipase Engineering Database，<a href="https://led.biocatnet.de/">https://led.biocatnet.de/</a>）中，选取α/β水解酶超家族8至12亚家族中各类氧阴离子空穴（oxyanion hole）类型的代表性蛋白质结构。研究人员提取了上述蛋白的N端结构域、C端结构域与核心结构域，并将其分别保存为独立的.pdb文件。随后借助Dali服务器（<a href="http://ekhidna2.biocenter.helsinki.fi/dali/">http://ekhidna2.biocenter.helsinki.fi/dali/</a>）的“全对全”结构比对工具，对这些结构域开展比对分析。在第二阶段，本研究使用Dali服务器的PDB（蛋白质数据库，Protein Data Bank）检索工具，将N端与C端结构域与PDB25数据库中的全部蛋白质结构进行比对。PDB25是对完整PDB数据库以25%的序列同一性阈值进行聚类后得到的子集。Dali服务器提供多种蛋白质结构相似性评估指标，其中Z值（Z-Score）是衡量结构相似性的核心指标：当Z值大于2时，即表明两个蛋白质结构存在显著相似性，对应相似的折叠模式。除Z值外，比对结果还包含均方根偏差（root-mean-square deviation，rmsd）以及序列同一性相关信息。