Systematic investigation of sequence and structural motifs that recognize ATP.
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.
School of Computer Science and Software Engineering, Tianjin Polytechnic University, Tianjin 300387, China. Electronic address: kchen1.tjpu@hotmail.com.
Ke
K
Chen
School of Computer Science and Software Engineering, Tianjin Polytechnic University, Tianjin 300387, China.
Dacheng
D
Wang
Department of Electrical and Computer Engineering, 2nd floor, ECERF (9107 116 Street), University of Alberta, Edmonton, AB T6G 2V4, Canada.
Lukasz
L
Kurgan
D000255:Adenosine Triphosphate / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment
D011506:Proteins; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D000604:Amino Acyl-tRNA Synthetases
ATP; Binding site; Sequence motif; Structural motif