title: Protein stabilizer, NDSB-195, enhances the dynamics of the β4 -α2 loop of ubiquitin.
abstract: Non-detergent sulfobetaines (NDSBs) are a new group of small, synthetic protein stabilizers, which have advantages over classical compatible osmolytes, such as polyol, amines, and amino acids: they do not increase solution viscosity, unlike polyols, and they are zwitterionic at all pH ranges, unlike amines and amino acids. NDSBs also facilitate the crystallization and refolding of proteins. The mechanism whereby NDSBs exhibit such activities, however, remains elusive. To gain insight into this mechanism, we studied, using nuclear magnetic resonance (NMR), the effects of dimethylethylammonium propane sulfonate (NDSB-195) on the dynamics of ubiquitin, on which a wealth of information has been accumulated. By analyzing the line width of amide proton resonances and the transverse relaxation rates of nitrogen atoms, we found that NDSB-195 enhances the microsecond-millisecond dynamics of a β4 -α2 loop of ubiquitin. Although those compounds that enhance protein dynamics are generally considered to destabilize protein molecules, NDSB-195 enhanced the stability of ubiquitin against guanidium chloride denaturation. Thus, the simultaneous enhancement of stability and flexibility by a single compound can be attained.
authors: Department of Molecular Science, Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma, 376-8515, Japan.
authors: Haimei
authors: H
authors: Wang
authors: Department of Molecular Science, Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma, 376-8515, Japan.
authors: Kazuo
authors: K
authors: Hosoda
authors: Department of Molecular Science, Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma, 376-8515, Japan.
authors: Takeshi
authors: T
authors: Ishii
authors: Department of Molecular Science, Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma, 376-8515, Japan.
authors: Ryo
authors: R
authors: Arai
authors: Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors: Toshiyuki
authors: T
authors: Kohno
authors: Department of Molecular Science, Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma, 376-8515, Japan.
authors: Shin-Ichi
authors: S
authors: Terawaki
authors: Department of Molecular Science, Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma, 376-8515, Japan.
authors: Kaori
authors: K
authors: Wakamatsu
mesh_terms: D001622:Betaine / Q000031:analogs & derivatives* / Q000737:chemistry; D019791:Guanidine / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D011522:Protons; D012996:Solutions; D025801:Ubiquitin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: C111794:NDSB 195; D011522:Protons; D012996:Solutions; D025801:Ubiquitin; D001622:Betaine; C483727:sulfobetaine; D019791:Guanidine
keywords: activation energy; chemical exchange; denaturation; flexibility; mechanism; microsecond-millisecond dynamics; non-detergent sulfobetaine; osmolyte; protein; stability