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Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus
by
Quang, Jenny Winjing
, Yu, Kunqian
, He, Chuan
, Qin, Guangrong
, Chen, Peter J.
, Yeo, Won-Sik
, Luan, Chi-Hao
, You, Qiancheng
, Cho, Hoonsik
, Bae, Taeok
, Ji, Quanjiang
, Wawrzak, Zdzislaw
, Luo, Guan-Zheng
, Hao, Ziyang
, Yang, Xiaojing
, Deng, Xin
, Weng, Xiaocheng
, Jiang, Hualiang
in
14/28
/ 38/91
/ 631/326/41/2536
/ 631/45/173
/ 631/45/275
/ 64/60
/ 82/80
/ 82/83
/ 96/95
/ 96/98
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ BASIC BIOLOGICAL SCIENCES
/ Benzophenones - pharmacology
/ Crystallography, X-Ray
/ Gene Expression Regulation, Bacterial - drug effects
/ Humanities and Social Sciences
/ multidisciplinary
/ Mutant Proteins - metabolism
/ Mutation - genetics
/ Protein Structure, Tertiary
/ Science
/ Science (multidisciplinary)
/ Signal Transduction - drug effects
/ Small Molecule Libraries - pharmacology
/ Staphylococcus aureus - genetics
/ Staphylococcus aureus - metabolism
/ Staphylococcus aureus - ultrastructure
/ Transcription, Genetic - drug effects
2016
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Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus
by
Quang, Jenny Winjing
, Yu, Kunqian
, He, Chuan
, Qin, Guangrong
, Chen, Peter J.
, Yeo, Won-Sik
, Luan, Chi-Hao
, You, Qiancheng
, Cho, Hoonsik
, Bae, Taeok
, Ji, Quanjiang
, Wawrzak, Zdzislaw
, Luo, Guan-Zheng
, Hao, Ziyang
, Yang, Xiaojing
, Deng, Xin
, Weng, Xiaocheng
, Jiang, Hualiang
in
14/28
/ 38/91
/ 631/326/41/2536
/ 631/45/173
/ 631/45/275
/ 64/60
/ 82/80
/ 82/83
/ 96/95
/ 96/98
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ BASIC BIOLOGICAL SCIENCES
/ Benzophenones - pharmacology
/ Crystallography, X-Ray
/ Gene Expression Regulation, Bacterial - drug effects
/ Humanities and Social Sciences
/ multidisciplinary
/ Mutant Proteins - metabolism
/ Mutation - genetics
/ Protein Structure, Tertiary
/ Science
/ Science (multidisciplinary)
/ Signal Transduction - drug effects
/ Small Molecule Libraries - pharmacology
/ Staphylococcus aureus - genetics
/ Staphylococcus aureus - metabolism
/ Staphylococcus aureus - ultrastructure
/ Transcription, Genetic - drug effects
2016
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Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus
by
Quang, Jenny Winjing
, Yu, Kunqian
, He, Chuan
, Qin, Guangrong
, Chen, Peter J.
, Yeo, Won-Sik
, Luan, Chi-Hao
, You, Qiancheng
, Cho, Hoonsik
, Bae, Taeok
, Ji, Quanjiang
, Wawrzak, Zdzislaw
, Luo, Guan-Zheng
, Hao, Ziyang
, Yang, Xiaojing
, Deng, Xin
, Weng, Xiaocheng
, Jiang, Hualiang
in
14/28
/ 38/91
/ 631/326/41/2536
/ 631/45/173
/ 631/45/275
/ 64/60
/ 82/80
/ 82/83
/ 96/95
/ 96/98
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ BASIC BIOLOGICAL SCIENCES
/ Benzophenones - pharmacology
/ Crystallography, X-Ray
/ Gene Expression Regulation, Bacterial - drug effects
/ Humanities and Social Sciences
/ multidisciplinary
/ Mutant Proteins - metabolism
/ Mutation - genetics
/ Protein Structure, Tertiary
/ Science
/ Science (multidisciplinary)
/ Signal Transduction - drug effects
/ Small Molecule Libraries - pharmacology
/ Staphylococcus aureus - genetics
/ Staphylococcus aureus - metabolism
/ Staphylococcus aureus - ultrastructure
/ Transcription, Genetic - drug effects
2016
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Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus
Journal Article
Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus
2016
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Overview
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.
The WalKR signal transduction system is involved in extracellular signal recognition, but the details of this function are not well established. Here, the authors report the crystal structure of this two-component system alongside the characterisation of a small-molecule activator.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/91
/ 64/60
/ 82/80
/ 82/83
/ 96/95
/ 96/98
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - metabolism
/ Benzophenones - pharmacology
/ Gene Expression Regulation, Bacterial - drug effects
/ Humanities and Social Sciences
/ Mutant Proteins - metabolism
/ Science
/ Signal Transduction - drug effects
/ Small Molecule Libraries - pharmacology
/ Staphylococcus aureus - genetics
/ Staphylococcus aureus - metabolism
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