Did protein kinase regulatory mechanisms evolve through elaboration of a simple structural component?

Kannan, N., Neuwald, A. F. (September 2005) Did protein kinase regulatory mechanisms evolve through elaboration of a simple structural component? J Mol Biol, 351 (5). pp. 956-72. ISSN 0022-2836 (Print)

URL: https://www.ncbi.nlm.nih.gov/pubmed/16051269
DOI: 10.1016/j.jmb.2005.06.057


Statistical analysis of the functional constraints acting on eukaryotic protein kinases (EPKs) and on distantly related kinases suggests that EPK regulatory mechanisms evolved around an ancient structural component whose most distinctive features include the HxD-motif adjoining the catalytic loop, the F-helix, an F-helix aspartate, and the DFG-motif adjoined to the activation loop. The HxD-histidine constitutes a convergence point for signal integration, as conserved interactions link it to key catalytic residues, to the F-helix aspartate, and to both ends of the DFG-motif. These and other conserved features appear to be associated with DFG conformational changes and with coordinated movements possibly associated with phosphate transfer and ADP release. The EPKs have acquired structural features that link this core component to likely substrate-interacting regions at either end of the F-helix (most notably involving an F-helix tryptophan) and to three regions undergoing conformational changes upon kinase activation: the activation segment, the C-helix, and the nucleotide-binding pocket.

Item Type: Paper
Uncontrolled Keywords: Adenosine Diphosphate chemistry Amino Acid Motifs Amino Acid Sequence Animals Binding Sites Databases Protein Evolution Molecular Glutamic Acid chemistry Histidine chemistry Humans Models Genetic Models Molecular Molecular Conformation Molecular Sequence Data Monte Carlo Method Protein Conformation Protein Kinases chemistry Protein Structure Tertiary Sequence Homology Amino Acid Tryptophan chemistry Tyrosine chemistry Water chemistry
Subjects: bioinformatics > computational biology
CSHL Authors:
Communities: CSHL labs > Neuwald lab
Depositing User: CSHL Librarian
Date: 2 September 2005
Date Deposited: 10 Jan 2012 19:14
Last Modified: 07 May 2018 18:23
Related URLs:
URI: https://repository.cshl.edu/id/eprint/22615

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