Sujatha M S, Balaji Petety V
School of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India.
Proteins. 2004 Apr 1;55(1):44-65. doi: 10.1002/prot.10612.
Galactose-binding proteins characterize an important subgroup of sugar-binding proteins that are involved in a variety of biological processes. Structural studies have shown that the Gal-specific proteins encompass a diverse range of primary and tertiary structures. The binding sites for galactose also seem to vary in different protein-galactose complexes. No common binding site features that are shared by the Gal-specific proteins to achieve ligand specificity are so far known. With the assumption that common recognition principles will exist for common substrate recognition, the present study was undertaken to identify and characterize any unique galactose-binding site signature by analyzing the three-dimensional (3D) structures of 18 protein-galactose complexes. These proteins belong to 7 nonhomologous families; thus, there is no sequence or structural similarity across the families. Within each family, the binding site residues and their relative distances were well conserved, but there were no similarities across families. A novel, yet simple, approach was adopted to characterize the binding site residues by representing their relative spatial dispositions in polar coordinates. A combination of the deduced geometrical features with the structural characteristics, such as solvent accessibility and secondary structure type, furnished a potential galactose-binding site signature. The signature was evaluated by incorporation into the program COTRAN to search for potential galactose-binding sites in proteins that share the same fold as the known galactose-binding proteins. COTRAN is able to detect galactose-binding sites with a very high specificity and sensitivity. The deduced galactose-binding site signature is strongly validated and can be used to search for galactose-binding sites in proteins. PROSITE-type signature sequences have also been inferred for galectin and C-type animal lectin-like fold families of Gal-binding proteins.
半乳糖结合蛋白是糖结合蛋白的一个重要亚群，参与多种生物学过程。结构研究表明，半乳糖特异性蛋白具有多种多样的一级和三级结构。半乳糖的结合位点在不同的蛋白质 - 半乳糖复合物中似乎也有所不同。目前尚不清楚半乳糖特异性蛋白为实现配体特异性而共享的共同结合位点特征。基于共同底物识别存在共同识别原则的假设，本研究通过分析18种蛋白质 - 半乳糖复合物的三维（3D）结构来鉴定和表征任何独特的半乳糖结合位点特征。这些蛋白质属于7个非同源家族；因此，各家族之间不存在序列或结构相似性。在每个家族中，结合位点残基及其相对距离是高度保守的，但各家族之间没有相似性。采用了一种新颖但简单的方法，通过在极坐标中表示结合位点残基的相对空间位置来对其进行表征。将推导的几何特征与结构特征（如溶剂可及性和二级结构类型）相结合，提供了一个潜在的半乳糖结合位点特征。通过将该特征纳入程序COTRAN来评估，以在与已知半乳糖结合蛋白具有相同折叠的蛋白质中搜索潜在的半乳糖结合位点。COTRAN能够以非常高的特异性和灵敏度检测半乳糖结合位点。推导的半乳糖结合位点特征得到了有力验证，可用于在蛋白质中搜索半乳糖结合位点。还为半乳糖凝集素和C型动物凝集素样折叠家族的半乳糖结合蛋白推断了PROSITE型特征序列。
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