Binkowski T Andrew, Joachimiak Andrzej, Liang Jie
Department of Bioengineering, The University of Illinois, 851 South Morgan St., Room 218, Chicago, IL 60607, USA.
Protein Sci. 2005 Dec;14(12):2972-81. doi: 10.1110/ps.051759005.
Structural genomics (SG) initiatives are expanding the universe of protein fold space by rapidly determining structures of proteins that were intentionally selected on the basis of low sequence similarity to proteins of known structure. Often these proteins have no associated biochemical or cellular functions. The SG success has resulted in an accelerated deposition of novel structures. In some cases the structural bioinformatics analysis applied to these novel structures has provided specific functional assignment. However, this approach has also uncovered limitations in the functional analysis of uncharacterized proteins using traditional sequence and backbone structure methodologies. A novel method, named pvSOAR (pocket and void Surface of Amino Acid Residues), of comparing the protein surfaces of geometrically defined pockets and voids was developed. pvSOAR was able to detect previously unrecognized and novel functional relationships between surface features of proteins. In this study, pvSOAR is applied to several structural genomics proteins. We examined the surfaces of YecM, BioH, and RpiB from Escherichia coli as well as the CBS domains from inosine-5'-monosphate dehydrogenase from Streptococcus pyogenes, conserved hypothetical protein Ta549 from Thermoplasm acidophilum, and CBS domain protein mt1622 from Methanobacterium thermoautotrophicum with the goal to infer information about their biochemical function.
结构基因组学（SG）计划正在通过快速确定基于与已知结构蛋白质的低序列相似性而特意选择的蛋白质结构，来扩展蛋白质折叠空间的范围。通常，这些蛋白质没有相关的生化或细胞功能。SG计划的成功导致了新结构的加速沉积。在某些情况下，应用于这些新结构的结构生物信息学分析提供了特定的功能归属。然而，这种方法也揭示了使用传统序列和主链结构方法对未表征蛋白质进行功能分析时的局限性。一种名为pvSOAR（氨基酸残基的口袋和空隙表面）的比较几何定义的口袋和空隙的蛋白质表面的新方法被开发出来。pvSOAR能够检测蛋白质表面特征之间以前未被识别的新功能关系。在这项研究中，pvSOAR被应用于几种结构基因组学蛋白质。我们检查了来自大肠杆菌的YecM、BioH和RpiB的表面，以及来自化脓性链球菌的肌苷-5'-单磷酸脱氢酶的CBS结构域、嗜热栖热菌的保守假设蛋白Ta549和嗜热自养甲烷杆菌的CBS结构域蛋白mt1622的表面，目的是推断它们生化功能的信息。
