Discovering structural motifs using a structural alphabet: application to magnesium-binding sites.
Discovering structural motifs using a structural alphabet: application to magnesium-binding sites.
复制标题
DOI：
10.1186/1471-2105-8-106
复制
发表时间：
2007-03-28
影响因子：
3
通讯作者：
Lim C
中科院分区：
文献类型：
--
作者：
Dudev M;Lim C
对于许多金属蛋白，尚未发现金属结合位点特征的序列基序，或者序列基序太短以致于它们不具有金属特异性。此类金属蛋白的显着例子是含有 Mg2+ 的金属蛋白，Mg2+ 是细胞生物化学中最通用的金属辅助因子之一。即使 Mg2+ 蛋白的序列同源性不足以识别 Mg2+ 特异性序列基序，它们在 Mg2+ 结合位点结构中仍可能具有相似性。然而，尚未报道 Mg2+ 结合位点的结构基序特征。因此，我们的目标是 (i) 开发一种通用方法，在给定 3D 蛋白质结构的情况下发现配体结合位点特征的结构模式/基序，以及 (ii) 将其应用于共享 <30% 序列同一性的 Mg2+ 蛋白质。我们的基序发现方法采用结构字母编码将 3D 结构转换为相应的 1D 结构字母序列，其中 Mg2+ 结构基序被识别为重复出现的结构模式。基于结构字母表的基序发现方法揭示了 Mg2+ 结合位点对某些局部/二级结构的结构偏好：与 Mg2+ 蛋白中的所有残基相比，第一和第二壳 Mg2+ 配体都更喜欢环而不是螺旋。即使 Mg2+ 蛋白没有显着的序列同源性，其中一些也具有相似的 Mg2+ 结合位点结构：发现了 4 个 Mg2+ 结构基序，占结合位点的 21%。特别是，发现的 Mg2+ 结构基序之一映射到特定的官能团，即水解酶。此外，其中 2 个基序未在非金属蛋白或 Ca2+ 结合蛋白中发现。因此发现的结构基序捕获了一些重要的生化和/或进化特性，因此可能有助于发现 Mg2+ 发挥重要生物学作用的蛋白质。本文提出的结构基序发现方法是通用的，可以应用于任何具有已知 3D 结构的蛋白质组。这种新方法及时考虑了越来越多的功能未知的蛋白质结构，这些蛋白质结构正在通过结构基因组学激励来解决。对于与已知功能的蛋白质没有显着序列同源性的此类蛋白质，映射到结构中特定蛋白质功能的结构基序的存在将表明可能的活性/结合位点和特定的生物功能。
For many metalloproteins, sequence motifs characteristic of metal-binding sites have not been found or are so short that they would not be expected to be metal-specific. Striking examples of such metalloproteins are those containing Mg2+, one of the most versatile metal cofactors in cellular biochemistry. Even when Mg2+-proteins share insufficient sequence homology to identify Mg2+-specific sequence motifs, they may still share similarity in the Mg2+-binding site structure. However, no structural motifs characteristic of Mg2+-binding sites have been reported. Thus, our aims are (i) to develop a general method for discovering structural patterns/motifs characteristic of ligand-binding sites, given the 3D protein structures, and (ii) to apply it to Mg2+-proteins sharing <30% sequence identity. Our motif discovery method employs structural alphabet encoding to convert 3D structures to the corresponding 1D structural letter sequences, where the Mg2+-structural motifs are identified as recurring structural patterns. The structural alphabet-based motif discovery method has revealed the structural preference of Mg2+-binding sites for certain local/secondary structures: compared to all residues in the Mg2+-proteins, both first and second-shell Mg2+-ligands prefer loops to helices. Even when the Mg2+-proteins share no significant sequence homology, some of them share a similar Mg2+-binding site structure: 4 Mg2+-structural motifs, comprising 21% of the binding sites, were found. In particular, one of the Mg2+-structural motifs found maps to a specific functional group, namely, hydrolases. Furthermore, 2 of the motifs were not found in non metalloproteins or in Ca2+-binding proteins. The structural motifs discovered thus capture some essential biochemical and/or evolutionary properties, and hence may be useful for discovering proteins where Mg2+ plays an important biological role. The structural motif discovery method presented herein is general and can be applied to any set of proteins with known 3D structures. This new method is timely considering the increasing number of structures for proteins with unknown function that are being solved from structural genomics incentives. For such proteins, which share no significant sequence homology to proteins of known function, the presence of a structural motif that maps to a specific protein function in the structure would suggest likely active/binding sites and a particular biological function.
登录
查看更多内容
影响因子：
14.9
作者：
Laskowski, RA
通讯作者：
Laskowski, RA
影响因子：
14.9
作者：
Tyagi M;Sharma P;Swamy CS;Cadet F;Srinivasan N;de Brevern AG;Offmann B
通讯作者：
Offmann B
影响因子：
11.4
作者：
CHOTHIA, C;LESK, AM
通讯作者：
LESK, AM
DOI：
10.1107/s0907444999007374
发表时间：
1999-08-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Harding, MM
通讯作者：
Harding, MM
影响因子：
5.1
作者：
Lahiri, Sushmita D.;Zhang, Guofeng;Allen, Karen N.
通讯作者：
Allen, Karen N.