Hrmova Maria, Fincher Geoffrey B
Australian Centre for Plant Functional Genomics, School of Agriculture, Food and Wine, University of Adelaide, Waite Campus, Glen Osmond, SA 5064, Australia.
Methods Mol Biol. 2009;513:199-227. doi: 10.1007/978-1-59745-427-8_11.
By mid-2007, the three-dimensional (3D) structures of some 45,000 proteins have been solved, over a period where the linear structures of millions of genes have been defined. Technical challenges associated with X-ray crystallography are being overcome and high-throughput methods both for crystallization of proteins and for solving their 3D structures are under development. The question arises as to how structural biology can be integrated with and adds value to functional genomics programs. Structural biology will assist in the definition of gene function through the identification of the likely function of the protein products of genes. The 3D information allows protein sequences predicted from DNA sequences to be classified into broad groups, according to the overall 'fold', or 3D shape, of the protein. Structural information can be used to predict the preferred substrate of a protein, and thereby greatly enhance the accurate annotation of the corresponding gene. Furthermore, it will enable the effects of amino acid substitutions in enzymes to be better understood with respect to enzyme function and could thereby provide insights into natural variation in genes. If the molecular basis of transcription factor-DNA interactions were defined through precise 3D knowledge of the protein-DNA binding site, it would be possible to predict the effects of base substitutions within the motif on the specificity and/or kinetics of binding. In this chapter, we present specific examples of how structural biology can provide valuable information for functional genomics programs.
到2007年年中，约45000种蛋白质的三维（3D）结构已得到解析，而在此期间，数百万个基因的线性结构已被确定。与X射线晶体学相关的技术挑战正在被克服，用于蛋白质结晶及其3D结构解析的高通量方法正在开发之中。于是就出现了一个问题，即结构生物学如何能与功能基因组学计划相结合并为其增添价值。结构生物学将通过确定基因蛋白质产物的可能功能来协助定义基因功能。3D信息能使根据DNA序列预测出的蛋白质序列依据蛋白质的整体“折叠”或3D形状被归类为大致的类别。结构信息可用于预测蛋白质的首选底物，从而极大地增强对相应基因的准确注释。此外，它将使人们能更好地理解酶中氨基酸替换对酶功能的影响，进而为洞察基因的自然变异提供线索。如果通过对蛋白质-DNA结合位点的精确3D知识确定转录因子-DNA相互作用的分子基础，就有可能预测基序内碱基替换对结合特异性和/或动力学的影响。在本章中，我们给出了结构生物学如何能为功能基因组学计划提供有价值信息的具体例子。
