Targeting Two-Component Signal Transduction: A Novel Drug Discovery System

Ario Okada, Yasuhiro Gotoh, Takafumi Watanabe, Eiji Furuta, Kaneyoshi Yamamoto, Ryutaro Utsumi

Research output: Chapter in Book/Report/Conference proceedingChapter

34 Citations (Scopus)

Abstract

We have developed two screening systems for isolating inhibitors that target bacterial two-component signal transduction: (1) a differential growth assay using a temperature-sensitive yycF mutant (CNM2000) of Bacillus subtilis, which is supersensitive to histidine kinase inhibitors, and (2) a high-throughput genetic system for targeting the homodimerization of histidine kinases essential for the bacterial two-component signal transduction. By using these methods, we have been able to identify various types of inhibitors that block the autophosphorylation of histidine kinases with different modes of actions.

Original languageEnglish
Title of host publicationTwo Component Signaling Systems, Part A
PublisherAcademic Press Inc.
Pages386-395
Number of pages10
DOIs
Publication statusPublished - Jan 1 2007
Externally publishedYes

Publication series

NameMethods in Enzymology
Volume422
ISSN (Print)0076-6879

Fingerprint

Signal transduction
Drug Discovery
Histidine
Signal Transduction
Phosphotransferases
Bacilli
Bacillus subtilis
Assays
Screening
Throughput
Temperature
Growth
Histidine Kinase

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Okada, A., Gotoh, Y., Watanabe, T., Furuta, E., Yamamoto, K., & Utsumi, R. (2007). Targeting Two-Component Signal Transduction: A Novel Drug Discovery System. In Two Component Signaling Systems, Part A (pp. 386-395). (Methods in Enzymology; Vol. 422). Academic Press Inc.. https://doi.org/10.1016/S0076-6879(06)22019-6

Targeting Two-Component Signal Transduction : A Novel Drug Discovery System. / Okada, Ario; Gotoh, Yasuhiro; Watanabe, Takafumi; Furuta, Eiji; Yamamoto, Kaneyoshi; Utsumi, Ryutaro.

Two Component Signaling Systems, Part A. Academic Press Inc., 2007. p. 386-395 (Methods in Enzymology; Vol. 422).

Research output: Chapter in Book/Report/Conference proceedingChapter

Okada, A, Gotoh, Y, Watanabe, T, Furuta, E, Yamamoto, K & Utsumi, R 2007, Targeting Two-Component Signal Transduction: A Novel Drug Discovery System. in Two Component Signaling Systems, Part A. Methods in Enzymology, vol. 422, Academic Press Inc., pp. 386-395. https://doi.org/10.1016/S0076-6879(06)22019-6
Okada A, Gotoh Y, Watanabe T, Furuta E, Yamamoto K, Utsumi R. Targeting Two-Component Signal Transduction: A Novel Drug Discovery System. In Two Component Signaling Systems, Part A. Academic Press Inc. 2007. p. 386-395. (Methods in Enzymology). https://doi.org/10.1016/S0076-6879(06)22019-6
Okada, Ario ; Gotoh, Yasuhiro ; Watanabe, Takafumi ; Furuta, Eiji ; Yamamoto, Kaneyoshi ; Utsumi, Ryutaro. / Targeting Two-Component Signal Transduction : A Novel Drug Discovery System. Two Component Signaling Systems, Part A. Academic Press Inc., 2007. pp. 386-395 (Methods in Enzymology).
@inbook{8b641673f8c9415da85a7197588e4729,
title = "Targeting Two-Component Signal Transduction: A Novel Drug Discovery System",
abstract = "We have developed two screening systems for isolating inhibitors that target bacterial two-component signal transduction: (1) a differential growth assay using a temperature-sensitive yycF mutant (CNM2000) of Bacillus subtilis, which is supersensitive to histidine kinase inhibitors, and (2) a high-throughput genetic system for targeting the homodimerization of histidine kinases essential for the bacterial two-component signal transduction. By using these methods, we have been able to identify various types of inhibitors that block the autophosphorylation of histidine kinases with different modes of actions.",
author = "Ario Okada and Yasuhiro Gotoh and Takafumi Watanabe and Eiji Furuta and Kaneyoshi Yamamoto and Ryutaro Utsumi",
year = "2007",
month = "1",
day = "1",
doi = "10.1016/S0076-6879(06)22019-6",
language = "English",
series = "Methods in Enzymology",
publisher = "Academic Press Inc.",
pages = "386--395",
booktitle = "Two Component Signaling Systems, Part A",
address = "United States",

}

TY - CHAP

T1 - Targeting Two-Component Signal Transduction

T2 - A Novel Drug Discovery System

AU - Okada, Ario

AU - Gotoh, Yasuhiro

AU - Watanabe, Takafumi

AU - Furuta, Eiji

AU - Yamamoto, Kaneyoshi

AU - Utsumi, Ryutaro

PY - 2007/1/1

Y1 - 2007/1/1

N2 - We have developed two screening systems for isolating inhibitors that target bacterial two-component signal transduction: (1) a differential growth assay using a temperature-sensitive yycF mutant (CNM2000) of Bacillus subtilis, which is supersensitive to histidine kinase inhibitors, and (2) a high-throughput genetic system for targeting the homodimerization of histidine kinases essential for the bacterial two-component signal transduction. By using these methods, we have been able to identify various types of inhibitors that block the autophosphorylation of histidine kinases with different modes of actions.

AB - We have developed two screening systems for isolating inhibitors that target bacterial two-component signal transduction: (1) a differential growth assay using a temperature-sensitive yycF mutant (CNM2000) of Bacillus subtilis, which is supersensitive to histidine kinase inhibitors, and (2) a high-throughput genetic system for targeting the homodimerization of histidine kinases essential for the bacterial two-component signal transduction. By using these methods, we have been able to identify various types of inhibitors that block the autophosphorylation of histidine kinases with different modes of actions.

UR - http://www.scopus.com/inward/record.url?scp=34447108830&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447108830&partnerID=8YFLogxK

U2 - 10.1016/S0076-6879(06)22019-6

DO - 10.1016/S0076-6879(06)22019-6

M3 - Chapter

C2 - 17628150

AN - SCOPUS:34447108830

T3 - Methods in Enzymology

SP - 386

EP - 395

BT - Two Component Signaling Systems, Part A

PB - Academic Press Inc.

ER -