Dokmanić Ivan, Sikić Mile, Tomić Sanja
Department of Electronic Systems and Information Processing, Faculty of Electrical Engineering and Computing, University of Zagreb, Unska 3, 10000 Zagreb, Croatia.
Acta Crystallogr D Biol Crystallogr. 2008 Mar;64(Pt 3):257-63. doi: 10.1107/S090744490706595X. Epub 2008 Feb 20.
Metal ions are constituents of many metalloproteins, in which they have either catalytic (metalloenzymes) or structural functions. In this work, the characteristics of various metals were studied (Cu, Zn, Mg, Mn, Fe, Co, Ni, Cd and Ca in proteins with known crystal structure) as well as the specificity of their environments. The analysis was performed on two data sets: the set of protein structures in the Protein Data Bank (PDB) determined with resolution <1.5 A and the set of nonredundant protein structures from the PDB. The former was used to determine the distances between each metal ion and its electron donors and the latter was used to assess the preferred coordination numbers and common combinations of amino-acid residues in the neighbourhood of each metal. Although the metal ions considered predominantly had a valence of two, their preferred coordination number and the type of amino-acid residues that participate in the coordination differed significantly from one metal ion to the next. This study concentrates on finding the specificities of a metal-ion environment, namely the distribution of coordination numbers and the amino-acid residue types that frequently take part in coordination. Furthermore, the correlation between the coordination number and the occurrence of certain amino-acid residues (quartets and triplets) in a metal-ion coordination sphere was analysed. The results obtained are of particular value for the identification and modelling of metal-binding sites in protein structures derived by homology modelling. Knowledge of the geometry and characteristics of the metal-binding sites in metalloproteins of known function can help to more closely determine the biological activity of proteins of unknown function and to aid in design of proteins with specific affinity for certain metals.
金属离子是许多金属蛋白的组成成分，在这些蛋白中它们具有催化（金属酶）或结构功能。在本研究中，我们研究了各种金属（已知晶体结构的蛋白质中的铜、锌、镁、锰、铁、钴、镍、镉和钙）的特性以及它们所处环境的特异性。分析是在两个数据集上进行的：蛋白质数据库（PDB）中分辨率小于1.5埃的蛋白质结构集，以及PDB中的非冗余蛋白质结构集。前者用于确定每个金属离子与其电子供体之间的距离，后者用于评估每个金属周围氨基酸残基的优选配位数和常见组合。尽管所考虑的金属离子主要具有二价，但它们的优选配位数以及参与配位的氨基酸残基类型在不同金属离子之间存在显著差异。本研究专注于寻找金属离子环境的特异性，即配位数的分布以及经常参与配位的氨基酸残基类型。此外，还分析了配位数与金属离子配位球中某些氨基酸残基（四重奏和三重奏）出现之间的相关性。所获得的结果对于通过同源建模推导的蛋白质结构中金属结合位点的识别和建模具有特别的价值。了解已知功能的金属蛋白中金属结合位点的几何形状和特性，有助于更精确地确定未知功能蛋白质的生物活性，并有助于设计对某些金属具有特定亲和力的蛋白质。
