CDC25A-inhibitory RE derivatives bind to pocket adjacent to the catalytic site

Ayako Tsuchiya; Miwako Asanuma; Go Hirai; Kana Oonuma; Muhammad Muddassar; Eri Nishizawa; Yusuke Koyama; Yuko Otani; Kam Y.J. Zhang; Mikiko Sodeoka

doi:10.1039/c3mb00003f

CDC25A-inhibitory RE derivatives bind to pocket adjacent to the catalytic site

Ayako Tsuchiya, Miwako Asanuma, Go Hirai, Kana Oonuma, Muhammad Muddassar, Eri Nishizawa, Yusuke Koyama, Yuko Otani, Kam Y.J. Zhang, Mikiko Sodeoka

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

RE derivatives, which are cell-permeable and non-electrophilic dual-specificity protein phosphatase inhibitors developed in our laboratory, inhibit CDC25A/B non-competitively, as determined by means of kinetic experiments. To identify the binding site of RE derivatives, we designed and synthesized the new probe molecule RE142, having a Michael acceptor functionality for covalent bond formation with the enzyme, a biotin tag to enable enrichment of probe-bound peptide(s), and a chemically cleavable linker to facilitate release of probe-bound peptides from avidin beads. LC-MS analysis indicated that RE142 binds to one of the residues Cys384-Tyr386 of CDC25A, within a pocket adjacent to the catalytic site.

Original language	English
Pages (from-to)	1026-1034
Number of pages	9
Journal	Molecular BioSystems
Volume	9
Issue number	5
DOIs	https://doi.org/10.1039/c3mb00003f
Publication status	Published - May 2013
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biotechnology
Molecular Biology

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10.1039/c3mb00003f

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title = "CDC25A-inhibitory RE derivatives bind to pocket adjacent to the catalytic site",

abstract = "RE derivatives, which are cell-permeable and non-electrophilic dual-specificity protein phosphatase inhibitors developed in our laboratory, inhibit CDC25A/B non-competitively, as determined by means of kinetic experiments. To identify the binding site of RE derivatives, we designed and synthesized the new probe molecule RE142, having a Michael acceptor functionality for covalent bond formation with the enzyme, a biotin tag to enable enrichment of probe-bound peptide(s), and a chemically cleavable linker to facilitate release of probe-bound peptides from avidin beads. LC-MS analysis indicated that RE142 binds to one of the residues Cys384-Tyr386 of CDC25A, within a pocket adjacent to the catalytic site.",

author = "Ayako Tsuchiya and Miwako Asanuma and Go Hirai and Kana Oonuma and Muhammad Muddassar and Eri Nishizawa and Yusuke Koyama and Yuko Otani and Zhang, {Kam Y.J.} and Mikiko Sodeoka",

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doi = "10.1039/c3mb00003f",

language = "English",

volume = "9",

pages = "1026--1034",

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publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - CDC25A-inhibitory RE derivatives bind to pocket adjacent to the catalytic site

AU - Tsuchiya, Ayako

AU - Asanuma, Miwako

AU - Hirai, Go

AU - Oonuma, Kana

AU - Muddassar, Muhammad

AU - Nishizawa, Eri

AU - Koyama, Yusuke

AU - Otani, Yuko

AU - Zhang, Kam Y.J.

AU - Sodeoka, Mikiko

PY - 2013/5

Y1 - 2013/5

N2 - RE derivatives, which are cell-permeable and non-electrophilic dual-specificity protein phosphatase inhibitors developed in our laboratory, inhibit CDC25A/B non-competitively, as determined by means of kinetic experiments. To identify the binding site of RE derivatives, we designed and synthesized the new probe molecule RE142, having a Michael acceptor functionality for covalent bond formation with the enzyme, a biotin tag to enable enrichment of probe-bound peptide(s), and a chemically cleavable linker to facilitate release of probe-bound peptides from avidin beads. LC-MS analysis indicated that RE142 binds to one of the residues Cys384-Tyr386 of CDC25A, within a pocket adjacent to the catalytic site.

AB - RE derivatives, which are cell-permeable and non-electrophilic dual-specificity protein phosphatase inhibitors developed in our laboratory, inhibit CDC25A/B non-competitively, as determined by means of kinetic experiments. To identify the binding site of RE derivatives, we designed and synthesized the new probe molecule RE142, having a Michael acceptor functionality for covalent bond formation with the enzyme, a biotin tag to enable enrichment of probe-bound peptide(s), and a chemically cleavable linker to facilitate release of probe-bound peptides from avidin beads. LC-MS analysis indicated that RE142 binds to one of the residues Cys384-Tyr386 of CDC25A, within a pocket adjacent to the catalytic site.

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CDC25A-inhibitory RE derivatives bind to pocket adjacent to the catalytic site

Abstract

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