Predicting protein function from structure: Unique structural features of proteases

被引:35
作者
Stawiski, EW
Baucom, AE
Lohr, SC
Gregoret, LM [1 ]
机构
[1] Univ Calif Santa Cruz, Dept Biol, Grad Program Mol Cellular & Dev Biol, Santa Cruz, CA 95064 USA
[2] Univ Calif Santa Cruz, Dept Comp Sci, Santa Cruz, CA 95064 USA
[3] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA
关键词
D O I
10.1073/pnas.070548997
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have noted consistent structural similarities among unrelated proteases. In comparison with other proteins of similar size, proteases have smaller than average surface areas, smaller radii of gyration, and higher C-alpha densities. These findings imply that proteases are, as a group, more tightly packed than other proteins. There are also notable differences in secondary structure content between these two groups of proteins: proteases have fewer helices and more loops. We speculate that both high packing density and low cu-helical content coevolved in proteases to avoid autolysis. By using the structural parameters that seem to show some separation between proteases and nonproteases, a neural network has been trained to predict protease function with over 86% accuracy. Moreover, it is possible to identify proteases whose folds were not represented during training. Similar structural analyses may be useful for identifying other classes of proteins and may be of great utility for categorizing the flood of structures soon to flow from structural genomics initiatives.
引用
收藏
页码:3954 / 3958
页数:5
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