Conformational Clusters of Phosphorylated Tyrosine.
Maha AbdelrasoulKomala PonniahAlice MaoMeghan S WardenWessam ElhefnawyYaohang LiSteven M PascalPublished in: Journal of the American Chemical Society (2017)
Tyrosine phosphorylation plays an important role in many cellular and intercellular processes including signal transduction, subcellular localization, and regulation of enzymatic activity. In 1999, Blom et al., using the limited number of protein data bank (PDB) structures available at that time, reported that the side chain structures of phosphorylated tyrosine (pY) are partitioned into two conserved conformational clusters ( Blom, N.; Gammeltoft, S.; Brunak, S. J. Mol. Biol. 1999 , 294 , 1351 - 1362 ). We have used the spectral clustering algorithm to cluster the increasingly growing number of protein structures with pY sites, and have found that the pY residues cluster into three distinct side chain conformations. Two of these pY conformational clusters associate strongly with a narrow range of tyrosine backbone conformation. The novel cluster also highly correlates with the identity of the n + 1 residue, and is strongly associated with a sequential pYpY conformation which places two adjacent pY side chains in a specific relative orientation. Further analysis shows that the three pY clusters are associated with distinct distributions of cognate protein kinases.
Keyphrases
- molecular dynamics simulations
- molecular dynamics
- single molecule
- high resolution
- amino acid
- protein protein
- binding protein
- machine learning
- magnetic resonance imaging
- hydrogen peroxide
- transcription factor
- computed tomography
- nitric oxide
- optical coherence tomography
- electronic health record
- big data
- deep learning
- single cell
- small molecule
- data analysis
- protein kinase