Your browser doesn't support javascript.
loading
Reduced efficacy of a Src kinase inhibitor in crowded protein solution.
Kasahara, Kento; Re, Suyong; Nawrocki, Grzegorz; Oshima, Hiraku; Mishima-Tsumagari, Chiemi; Miyata-Yabuki, Yukako; Kukimoto-Niino, Mutsuko; Yu, Isseki; Shirouzu, Mikako; Feig, Michael; Sugita, Yuji.
Afiliación
  • Kasahara K; Laboratory for Biomolecular Function Simulation, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
  • Re S; Laboratory for Biomolecular Function Simulation, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
  • Nawrocki G; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
  • Oshima H; Laboratory for Biomolecular Function Simulation, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
  • Mishima-Tsumagari C; Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan.
  • Miyata-Yabuki Y; Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan.
  • Kukimoto-Niino M; Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan.
  • Yu I; Department of Life Science and Informatics, Maebashi Institute of Technology, Kamisadori-machi, Maebashi, Gunma, Japan.
  • Shirouzu M; Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan.
  • Feig M; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA. mfeiglab@gmail.com.
  • Sugita Y; Laboratory for Biomolecular Function Simulation, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan. sugita@riken.jp.
Nat Commun ; 12(1): 4099, 2021 07 02.
Article en En | MEDLINE | ID: mdl-34215742
The inside of a cell is highly crowded with proteins and other biomolecules. How proteins express their specific functions together with many off-target proteins in crowded cellular environments is largely unknown. Here, we investigate an inhibitor binding with c-Src kinase using atomistic molecular dynamics (MD) simulations in dilute as well as crowded protein solution. The populations of the inhibitor, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1), in bulk solution and on the surface of c-Src kinase are reduced as the concentration of crowder bovine serum albumins (BSAs) increases. This observation is consistent with the reduced PP1 inhibitor efficacy in experimental c-Src kinase assays in addition with BSAs. The crowded environment changes the major binding pathway of PP1 toward c-Src kinase compared to that in dilute solution. This change is explained based on the population shift mechanism of local conformations near the inhibitor binding site in c-Src kinase.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas / Familia-src Quinasas / Inhibidores de Proteínas Quinasas Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas / Familia-src Quinasas / Inhibidores de Proteínas Quinasas Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido