title: High-resolution X-ray analysis reveals binding of arginine to aromatic residues of lysozyme surface: implication of suppression of protein aggregation by arginine.
abstract: While biotechnological applications of arginine (Arg) as a solution additive that prevents protein aggregation are increasing, the molecular mechanism of its effects remains unclear. In this study, we investigated the Arg-lysozyme complex by high-resolution crystallographic analysis. Three Arg molecules were observed to be in close proximity to aromatic amino acid residues of the protein surface, and their occupancies gradually increased with increasing Arg concentration. These interactions were mediated by electrostatic, hydrophobic and cation-π interactions with the surface residues. The binding of Arg decreased the accessible surface area of aromatic residues by 40%, but increased that of charged residues by 10%. These changes might prevent intermolecular hydrophobic interactions by shielding hydrophobic regions of the lysozyme surface, resulting in an increase in protein solubility.
authors.affiliation: Japan Synchrotron Radiation Research Institute (SPring-8), 1-1-1 Kouto, Sayo, Hyogo 679-5198, Japan. l-ito@spring8.or.jp
authors.forename: Len
authors.initials: L
authors.lastname: Ito
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shiraki
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsuura
authors.forename: Masaki
authors.initials: M
authors.lastname: Okumura
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Seiki
authors.initials: S
authors.lastname: Baba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumasaka
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D012995:Solubility; D013050:Spectrometry, Fluorescence
chemical_list: D001120:Arginine; D009113:Muramidase