Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2

The protein tyrosine phosphatase SHP2 is a key regulator of cell cycle control. Here the authors combine NMR measurements and X-ray crystallography and show that wild-type SHP2 dynamically exchanges between a closed inactive conformation and an open activated form and that the oncogenic E76K mutatio...

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Autores principales:	Ricardo A. P. Pádua, Yizhi Sun, Ingrid Marko, Warintra Pitsawong, John B. Stiller, Renee Otten, Dorothee Kern
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/77cc04b8724e47ce9663728a803fea11
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spelling	oai:doaj.org-article:77cc04b8724e47ce9663728a803fea112021-12-02T15:34:49ZMechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP210.1038/s41467-018-06814-w2041-1723https://doaj.org/article/77cc04b8724e47ce9663728a803fea112018-10-01T00:00:00Zhttps://doi.org/10.1038/s41467-018-06814-whttps://doaj.org/toc/2041-1723The protein tyrosine phosphatase SHP2 is a key regulator of cell cycle control. Here the authors combine NMR measurements and X-ray crystallography and show that wild-type SHP2 dynamically exchanges between a closed inactive conformation and an open activated form and that the oncogenic E76K mutation shifts the equilibrium to the open state, which is reversed by binding of the allosteric inhibitor SHP099.Ricardo A. P. PáduaYizhi SunIngrid MarkoWarintra PitsawongJohn B. StillerRenee OttenDorothee KernNature PortfolioarticleScienceQENNature Communications, Vol 9, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Ricardo A. P. Pádua Yizhi Sun Ingrid Marko Warintra Pitsawong John B. Stiller Renee Otten Dorothee Kern Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2
description	The protein tyrosine phosphatase SHP2 is a key regulator of cell cycle control. Here the authors combine NMR measurements and X-ray crystallography and show that wild-type SHP2 dynamically exchanges between a closed inactive conformation and an open activated form and that the oncogenic E76K mutation shifts the equilibrium to the open state, which is reversed by binding of the allosteric inhibitor SHP099.
format	article
author	Ricardo A. P. Pádua Yizhi Sun Ingrid Marko Warintra Pitsawong John B. Stiller Renee Otten Dorothee Kern
author_facet	Ricardo A. P. Pádua Yizhi Sun Ingrid Marko Warintra Pitsawong John B. Stiller Renee Otten Dorothee Kern
author_sort	Ricardo A. P. Pádua
title	Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2
title_short	Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2
title_full	Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2
title_fullStr	Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2
title_full_unstemmed	Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2
title_sort	mechanism of activating mutations and allosteric drug inhibition of the phosphatase shp2
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/77cc04b8724e47ce9663728a803fea11
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Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2

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