Statistical modeling and analysis of the LAGLIDADG family of site-specific endonucleases and identification of an intein that encodes a site-specific endonuclease of the HNH family
Statistical modeling and analysis of the LAGLIDADG family of site-specific endonucleases and identification of an intein that encodes a site-specific endonuclease of the HNH family
复制标题
DOI：
10.1093/nar/25.22.4626
复制
发表时间：
1997-11-15
影响因子：
14.9
通讯作者：
Mian, IS
中科院分区：
文献类型：
--
作者：
Dalgaard, JZ;Klar, AJ;Mian, IS
由病毒、噬菌体以及古细菌、真核细胞核和细胞器基因组编码的位点特异性DNA内切酶的LAGLIDADG和HNH家族的特征分别在于序列基序“LAGLIDADG”和“HNH”。这些内切酶已被证明存在于不同的环境中：LAGLIDADG内切酶被发现于内含肽、古细菌和I组内含子中，并作为独立的开放阅读框架（ORF）; HNH核酸内切酶存在于I组和II组内含子中并作为ORF。在此，已经创建了涵盖这些家族的保守基序和更多可变区的统计模型（隐马尔可夫模型，HNH），并用于表征已知的和潜在的新家族成员。已经鉴定了许多新的推定的LAGLIDADG和HNH核酸内切酶，包括内含肽编码的HNH序列。对130个LAGLIDADG家族成员和I-CreI核酸内切酶的三维结构的HMM生成的多重比对的分析使得能够定义重复结构域的核心元件（类似于90个残基），一个保守的带负电荷的残基被认为参与催化，两个科的系统发育分析表明，不同的移动的元素之间缺乏核酸内切酶的交换（环境）和来自不同系统发育王国的宿主之间，然而，在相同类型的元件之间，核酸内切酶结构域似乎发生了相当大的交换，这类事件被认为对于新特异性元件的形成是重要的。
The LAGLIDADG and HNH families of site-specific DNA endonucleases encoded by viruses, bacteriophages as well as archaeal, eucaryotic nuclear and organellar genomes are characterized by the sequence motifs 'LAGLIDADG' and 'HNH', respectively, These endonucleases have been shown to occur in different environments: LAGILIDADG endonucleases are found in inteins, archaeal and group I introns and as free standing open reading frames (ORFs); HNH endonucleases occur in group I and group II introns and as ORFs, Here, statistical models (hidden Markov models, HMMs) that encompass both the conserved motifs and more variable regions of these families have been created and employed to characterize known and potential new family members, A number of new, putative LAGLIDADG and HNH endonucleases have been identified including an intein-encoded HNH sequence. Analysis of an HMM-generated multiple alignment of 130 LAGLIDADG family members and the th ree-dimensional structure of the I-CreI endonuclease has enabled definition of the core elements of the repeated domain (similar to 90 residues) that is present in this family of proteins, A conserved negatively charged residue is proposed to be involved in catalysis, Phylogenetic analysis of the two families indicates a lack of exchange of endonucleases between different mobile elements (environments) and between hosts from different phylogenetic kingdoms, However, there does appear to have been considerable exchange of endonuclease domains amongst elements of the same type, Such events are suggested to be important for the formation of elements of new specficity.