Arginine-aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation

Shah, Dhawal
Li, Jianguo
Shaikh, Abdul Rajjak
Rajagopalan, Raj
We examine the interaction of aromatic residues of proteins with arginine, an additive commonly used to suppress protein aggregation, using experiments and molecular dynamics simulations. An aromatic-rich peptide, FFYTP (a segment of insulin), and lysozyme and insulin are used as model systems. Mass spectrometry shows that arginine increases the solubility of FFYTP by binding to the peptide, with the simulations revealing the predominant association of arginine to be with the aromatic residues. The calculations further show a positive preferential interaction coefficient, GXP, contrary to conventional thinking that positive GXP's indicate aggregation rather than suppression of aggregation. Simulations with lysozyme and insulin also show arginine's preference for aromatic residues, in addition to acidic residues. We use these observations and earlier results reported by us and others to discuss the possible implications of arginine's interactions with aromatic residues on the solubilization of aromatic moieties and proteins. Our results also highlight the fact that explanations based purely on GXP, which measures average affinity of an additive to a protein, could obscure or misinterpret the underlying molecular mechanisms behind additive-induced suppression of protein aggregation. (c) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012


GPCR-Gα protein precoupling: Interaction between Ste2p, a yeast GPCR, and Gpa1p, its Gα protein, is formed before ligand binding via the Ste2p C-terminal domain and the Gpa1p N-terminal domain
Cevheroğlu, Orkun; Becker, Jeffrey M.; Son, Çağdaş Devrim (Elsevier BV, 2017-12)
G protein coupled receptors bind ligands that initiate intracellular signaling cascades via heterotrimeric G proteins. In this study, involvement of the N-terminal residues of yeast G-alpha (Gpa1p) with the C-terminal residues of a full-length or C-terminally truncated Ste2p were investigated using bioluminescence resonance energy transfer (BRET), a non-radiative energy transfer phenomenon where protein-protein interactions can be quantified between a donor bioluminescent molecule and a suitable acceptor fl...
Isoquinolinedione-urea hybrids: Synthesis, antibacterial evaluation, drug-likeness, molecular docking and DFT studies
In the present study, we applied the molecular hybridization approach to combine isoquinolinedione and urea pharmacophores in the same molecules. The hybrid compounds (IU1-IU14) were obtained by the reaction of 2-aminohomophthalimide and an equivalent amount of various isocyanate derivatives. After confirming the chemical structures and evaluating drug-likeness properties, the synthesized compounds were examined for their antibacterial activities against a wide range of bacteria. The compounds possessing li...
Immobilization of glucose oxidase in poly(2-hydroxyethyl methacrylate) membranes
Arica, Y.; Hasirci, V.N.; Arica, Yakup (Elsevier BV, 1987-11)
Glucose oxidase (GOD) was immobilized in a poly(2-hydroxyethyl methacrylate) (HEMA) membrane through matrix entrapment in order to investigate the effect of various parameters (e.g. concentration of ingredients, temperature, repeated interaction with glucose and shelf storage) on the activity of the enzyme. Permeability of the membrane to a model permeant was tested and SEMs were obtained. It was observed that upon immobilization the affinity of GOD towards glucose was substantially decreased, and increasin...
Aromatic amino acid synthesis performance of bacillus acidocaldarius
Kocabaş, Pınar; Çalık, Pınar; Department of Chemical Engineering (2004)
In this study, the effects of bioprocess operation parameters on aromatic amino acid synthesis performance of Bacillus acidocaldarius were investigated. Firstly, in laboratory scale shake-bioreactors, a defined medium was designed in terms of its carbon and nitrogen sources, to achieve the highest cell concentration. Thereafter, the effects of bioprocess operation parameters, i.e., pH and temperature were investigated; and the optimum medium contained (kg m-3): fructose, 8; (NH4)2HPO4, 5; CaCl2, 0.2; KH2PO4...
Amino acid substitution matrices based on 4-body Delaunay contact profiles
Sacan, Ahmet; Toroslu, İsmail Hakkı (2007-10-17)
Sequence similarity search of proteins is one of the basic and most common steps followed in bioninformatics research and is used in making evolutionary, structural, and functional inferences. The quality of the search and the alignment of the protein sequences depend crucially on the underlying amino-acid substitution matrix. We present a method for deriving amino acid substitution matrices from 4-body contact propensities of amino-acids in 3D protein structures. Unlike current popular methods, our method ...
Citation Formats
D. Shah, J. Li, A. R. Shaikh, and R. Rajagopalan, “Arginine-aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation,” BIOTECHNOLOGY PROGRESS, pp. 223–231, 2012, Accessed: 00, 2020. [Online]. Available: