The Mighty Arginine, the Stable Quaternary Amines, the Powerful Aromatics, and the Aggressive Phosphate: Their Role in the Noncovalent Minuet
- 12 March 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Proteome Research
- Vol. 3 (3) , 478-484
- https://doi.org/10.1021/pr034091l
Abstract
In the age of proteomics, the role of certain amino acid residues and some post-translational modifications in noncovalent complex formation are gaining in importance, as the understanding of interactions between biological molecules, is at the heart of the structure function relationship puzzle. In this work, mass spectrometry is used to highlight ammonium− or guanidinium−aromatic interactions through Cation-π bonds and ammonium− or guanidinium−phosphate interactions through salt bridge formation. Such interactions are crucial factors in certain ligand−receptor interactions and receptor−receptor interactions. In addition, the ability of phosphorylated residues and phosphorylated lipids to form noncovalent complexes with guanidinium and quaternary ammonium (mostly through Coulombic interactions) is demonstrated, and could explain the stability of certain membrane embedded protein, or a possible role for phosphorylation in protein−protein interactions. Dougherty's work demonstrates cation−π interactions in intra-protein interactions and folding, the present work explores inter-peptide interactions, i.e., the formation of noncovalent complexes between peptides' epitopes containing adjacent aromatic residues and ones containing adjacent Arg as a model to better understand the role of cation-π complexes in protein−protein interaction. Complexes of peptides containing aromatic residues with quaternary amines as well as the interaction of aromatic compounds, with the guanidinium group of Arg are also investigated. Considering that an inordinate number of therapeutic compounds contain aromatic rings and quaternary amines, the above-described interactions could possibly be of great importance in better understanding their mechanism of action. Keywords: noncovalent interactions • quaternary amines • phosphate moietiesKeywords
This publication has 25 references indexed in Scilit:
- Investigation of sample preparation and instrumental parameters in the matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry of noncovalent peptide/peptide complexesRapid Communications in Mass Spectrometry, 2003
- Hydrophobicity of transmembrane proteins: Spatially profiling the distributionProtein Science, 2003
- A Perturbed pKa at the Binding Site of the Nicotinic Acetylcholine Receptor: Implications for Nicotine BindingJournal of the American Chemical Society, 2002
- Cation−π Interactions and the Gas-Phase Thermochemistry of the Na+/Phenylalanine ComplexJournal of the American Chemical Society, 2001
- The Role of Cation−π Interactions in Biomolecular Association. Design of Peptides Favoring Interactions between Cationic and Aromatic Amino Acid Side ChainsJournal of the American Chemical Society, 2001
- Interactions of Phenol and Indole with Metal Ions in the Gas Phase: Models For Tyr and Trp Side-Chain BindingJournal of the American Chemical Society, 1999
- Topology of ligand binding sites on the nicotinic acetylcholine receptorBrain Research Reviews, 1997
- Role of Aromatic Transmembrane Residues of the δ-Opioid Receptor in Ligand RecognitionJournal of Biological Chemistry, 1996
- Cation-π Interactions in Chemistry and Biology: A New View of Benzene, Phe, Tyr, and TrpScience, 1996
- Matrix-Assisted Laser Desorption/Ionization of Noncovalently Bound CompoundsAnalytical Chemistry, 1995