Chen Ke, Wang Dacheng, Kurgan Lukasz
School of Computer Science and Software Engineering, Tianjin Polytechnic University, Tianjin 300387, China.
School of Computer Science and Software Engineering, Tianjin Polytechnic University, Tianjin 300387, China.
Comput Biol Chem. 2015 Jun;56:131-41. doi: 10.1016/j.compbiolchem.2015.04.008. Epub 2015 Apr 20.
Interaction between ATP, a multifunctional and ubiquitous nucleotide, and proteins initializes phosphorylation, polypeptide synthesis and ATP hydrolysis which supplies energy for metabolism. However, current knowledge concerning the mechanisms through which ATP is recognized by proteins is incomplete, scattered, and inaccurate. We systemically investigate sequence and structural motifs of proteins that recognize ATP. We identified three novel motifs and refined the known p-loop and class II aminoacyl-tRNA synthetase motifs. The five motifs define five distinct ATP-protein interaction modes which concern over 5% of known protein structures. We demonstrate that although these motifs share a common GXG tripeptide they recognize ATP through different functional groups. The p-loop motif recognizes ATP through phosphates, class II aminoacyl-tRNA synthetase motif targets adenosine and the other three motifs recognize both phosphates and adenosine. We show that some motifs are shared by different enzyme types. Statistical tests demonstrate that the five sequence motifs are significantly associated with the nucleotide binding proteins. Large-scale test on PDB reveals that about 98% of proteins that include one of the structural motifs are confirmed to bind ATP.
多功能且普遍存在的核苷酸ATP与蛋白质之间的相互作用引发磷酸化、多肽合成以及为新陈代谢提供能量的ATP水解。然而，目前关于蛋白质识别ATP的机制的知识并不完整、零散且不准确。我们系统地研究了识别ATP的蛋白质的序列和结构基序。我们鉴定出三个新的基序，并完善了已知的P环和II类氨酰-tRNA合成酶基序。这五个基序定义了五种不同的ATP-蛋白质相互作用模式，涉及超过5%的已知蛋白质结构。我们证明，尽管这些基序共享一个共同的GXG三肽，但它们通过不同的官能团识别ATP。P环基序通过磷酸基团识别ATP，II类氨酰-tRNA合成酶基序靶向腺苷，其他三个基序同时识别磷酸基团和腺苷。我们表明，一些基序为不同的酶类型所共有。统计测试表明，这五个序列基序与核苷酸结合蛋白显著相关。对蛋白质数据库（PDB）的大规模测试表明，约98%包含其中一个结构基序的蛋白质被证实能结合ATP。
