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Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus.
Ji, Quanjiang; Chen, Peter J; Qin, Guangrong; Deng, Xin; Hao, Ziyang; Wawrzak, Zdzislaw; Yeo, Won-Sik; Quang, Jenny Winjing; Cho, Hoonsik; Luo, Guan-Zheng; Weng, Xiaocheng; You, Qiancheng; Luan, Chi-Hao; Yang, Xiaojing; Bae, Taeok; Yu, Kunqian; Jiang, Hualiang; He, Chuan.
Afiliação
  • Ji Q; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • Chen PJ; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • Qin G; State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Deng X; Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.
  • Hao Z; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • Wawrzak Z; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • Yeo WS; Synchrotron Research Center, LS-CAT, Northwestern University, Argonne, Illinois 60439, USA.
  • Quang JW; Indiana University School of Medicine-Northwest, Gary, Indiana 46408, USA.
  • Cho H; High-Throughput Analysis Laboratory, Department of Molecular Biosciences, Center for Structural Genomics of Infectious Diseases, Northwestern University, Evanston, Illinois 60208, USA.
  • Luo GZ; Indiana University School of Medicine-Northwest, Gary, Indiana 46408, USA.
  • Weng X; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • You Q; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • Luan CH; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • Yang X; High-Throughput Analysis Laboratory, Department of Molecular Biosciences, Center for Structural Genomics of Infectious Diseases, Northwestern University, Evanston, Illinois 60208, USA.
  • Bae T; Department of Biochemistry and Molecular Biology, University of Chicago, 929 E 57th Street, Chicago, Illinois 60637, USA.
  • Yu K; Indiana University School of Medicine-Northwest, Gary, Indiana 46408, USA.
  • Jiang H; State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • He C; State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Nat Commun ; 7: 11000, 2016 Mar 18.
Article em En | MEDLINE | ID: mdl-26987594
ABSTRACT
Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase 'WalK' (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resulted in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. The molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Staphylococcus aureus / Proteínas de Bactérias / Transdução de Sinais Tipo de estudo: Prognostic_studies Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Staphylococcus aureus / Proteínas de Bactérias / Transdução de Sinais Tipo de estudo: Prognostic_studies Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos