title: Glycine amide shielding on the aromatic surfaces of lysozyme: implication for suppression of protein aggregation.
abstract: Glycine amide (GlyAd), a typically amidated amino acid, is a versatile additive that suppresses protein aggregation during refolding, heat treatment, and crystallization. In spite of its effectiveness, the exact mechanism by which GlyAd suppresses protein aggregation remains to be elucidated. Here, we show the crystal structure of the GlyAd-lysozyme complex by high resolution X-ray crystallographic analysis at a 1.05Å resolution. GlyAd bound to the lysozyme surface near aromatic residues and decreased the amount of bound waters and increased the mobility of protein. Arg and GlyAd molecules are different in binding sites and patterns from glycerol and related compounds, indicating that decreasing hydrophobic patches might be involved in suppression of protein aggregation.
authors.affiliation: Japan Synchrotron Radiation Research Institute (SPring-8), Sayo, Hyogo, 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: Masatomo
authors.initials: M
authors.lastname: Makino
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumasaka
mesh_terms: D024322:Amino Acids, Aromatic / Q000737:chemistry; D000818:Animals; D001120:Arginine / Q000737:chemistry; D002645:Chickens; D018360:Crystallography, X-Ray; D004527:Egg Proteins / Q000737:chemistry*; D004795:Enzyme Stability / Q000187:drug effects*; D005990:Glycerol / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008968:Molecular Conformation; D009113:Muramidase / Q000737:chemistry*; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D011485:Protein Binding; D011489:Protein Denaturation; D012995:Solubility / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D024322:Amino Acids, Aromatic; D004527:Egg Proteins; D011310:Preservatives, Pharmaceutical; D014867:Water; C018556:glycine amide; D001120:Arginine; C421864:hen egg lysozyme; D009113:Muramidase; D005990:Glycerol; D005998:Glycine