Structural and evolutionary classification of Type II restriction enzymes based on theoretical and experimental analyses.
Structural and evolutionary classification of Type II restriction enzymes based on theoretical and experimental analyses.
复制标题
DOI：
10.1093/nar/gkn175
复制
发表时间：
2008-06
影响因子：
14.9
通讯作者：
Bujnicki JM
中科院分区：
文献类型：
--
作者：
Orlowski J;Bujnicki JM
很长一段时间以来，II型限制性内切酶一直是ORFans的典范：蛋白质之间没有可检测到的相似性，也没有与数据库中任何其他蛋白质的相似性，尽管它们具有共同的细胞和生化功能。截至2008年1月发表的结晶学分析仅为限制酶数据库(REBASE)中可用的1637个II型Rease序列中的28个提供了高分辨率结构。在这些结构中，除两个外，其余都具有催化结构域，具有共同的Pd-(D/E)XK核酸酶折叠。有两个结构与其他结构无关：R.BfiI显示磷脂酶D(PLD)折叠，而R.PabI有一个新的折叠称为‘半管’。到目前为止，在定点突变的支持下，生物信息学研究已经将初步分配的Rease折叠的数量扩大到5个(现在还包括早些时候在归巢内切酶中发现的GIY-YIG和HNH折叠)，并提供了数十个没有实验解决结构的Rease序列的结构预测。在这里，我们对REBASE中所有可用的II型Rease序列及其在NCBI的非冗余和环境样本数据库中可检测到的同源序列进行了全面的研究。我们对早期报道的结构分配和预测进行了总结和批判性评估，对所有Rease序列进行了新的家族分类，进行了结构域结构分析，并对三维折叠进行了新的预测。在289个实验描述的(不是推测的)类型II酶中，我们指定199个(69%)包含PD-(D/E)XK结构域，其明显的全长序列可在REBASE中获得。HNH域是第二常见的，有24个(8%)成员。当考虑可能的折射率时，Pd-(D/E)XK和HNH折叠的比例分别为48%和30%。56个特征的(和521个预测的)折叠层仍然没有被分配到到目前为止识别的五个折叠层中的任何一个，并且可能表现出新的架构。这些酶被认为是通过高分辨实验方法确定结构的最有趣的靶标。我们的分析提供了第一张II型酶之间序列-结构关系的全面图谱，并将有助于集中这一大类具有生物技术重要性的酶的结构和功能基因组学的努力。
For a very long time, Type II restriction enzymes (REases) have been a paradigm of ORFans: proteins with no detectable similarity to each other and to any other protein in the database, despite common cellular and biochemical function. Crystallographic analyses published until January 2008 provided high-resolution structures for only 28 of 1637 Type II REase sequences available in the Restriction Enzyme database (REBASE). Among these structures, all but two possess catalytic domains with the common PD-(D/E)XK nuclease fold. Two structures are unrelated to the others: R.BfiI exhibits the phospholipase D (PLD) fold, while R.PabI has a new fold termed ‘half-pipe’. Thus far, bioinformatic studies supported by site-directed mutagenesis have extended the number of tentatively assigned REase folds to five (now including also GIY-YIG and HNH folds identified earlier in homing endonucleases) and provided structural predictions for dozens of REase sequences without experimentally solved structures. Here, we present a comprehensive study of all Type II REase sequences available in REBASE together with their homologs detectable in the nonredundant and environmental samples databases at the NCBI. We present the summary and critical evaluation of structural assignments and predictions reported earlier, new classification of all REase sequences into families, domain architecture analysis and new predictions of three-dimensional folds. Among 289 experimentally characterized (not putative) Type II REases, whose apparently full-length sequences are available in REBASE, we assign 199 (69%) to contain the PD-(D/E)XK domain. The HNH domain is the second most common, with 24 (8%) members. When putative REases are taken into account, the fraction of PD-(D/E)XK and HNH folds changes to 48% and 30%, respectively. Fifty-six characterized (and 521 predicted) REases remain unassigned to any of the five REase folds identified so far, and may exhibit new architectures. These enzymes are proposed as the most interesting targets for structure determination by high-resolution experimental methods. Our analysis provides the first comprehensive map of sequence-structure relationships among Type II REases and will help to focus the efforts of structural and functional genomics of this large and biotechnologically important class of enzymes.
登录
查看更多内容
影响因子：
14.9
作者：
Cheng, J;Randall, AZ;Sweredoski, MJ;Baldi, P
通讯作者：
Baldi, P
影响因子：
4.4
作者：
Feder M;Bujnicki JM
通讯作者：
Bujnicki JM
影响因子：
13.8
作者：
Bujnicki, JM;Radlinska, M;Rychlewski, L
通讯作者：
Rychlewski, L
影响因子：
3.2
作者：
Anton, BP;Raleigh, EA
通讯作者：
Raleigh, EA
DOI：
10.1038/79032
发表时间：
2000-09-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Deibert, M;Grazulis, S;Huber, R
通讯作者：
Huber, R