Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)

The tumor suppressor p53 is mutated in more than half of human cancers and the compound methylene quinuclidinone (MQ) was shown to reactivate p53 mutants by binding covalently to cysteine residues. Here, the authors present crystal structures of wild-type and cancer related p53 mutant core domains b...

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Autores principales:	Oksana Degtjarik, Dmitrij Golovenko, Yael Diskin-Posner, Lars Abrahmsén, Haim Rozenberg, Zippora Shakked
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/61ab66026ad342f6901e1b078e2ffc95
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spelling	oai:doaj.org-article:61ab66026ad342f6901e1b078e2ffc952021-12-05T12:22:43ZStructural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)10.1038/s41467-021-27142-62041-1723https://doaj.org/article/61ab66026ad342f6901e1b078e2ffc952021-12-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-27142-6https://doaj.org/toc/2041-1723The tumor suppressor p53 is mutated in more than half of human cancers and the compound methylene quinuclidinone (MQ) was shown to reactivate p53 mutants by binding covalently to cysteine residues. Here, the authors present crystal structures of wild-type and cancer related p53 mutant core domains bound to MQ alone and in complex with their DNA response elements and observe that MQ is bound to several cysteine residues located at the surface of the core domain.Oksana DegtjarikDmitrij GolovenkoYael Diskin-PosnerLars AbrahmsénHaim RozenbergZippora ShakkedNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Oksana Degtjarik Dmitrij Golovenko Yael Diskin-Posner Lars Abrahmsén Haim Rozenberg Zippora Shakked Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)
description	The tumor suppressor p53 is mutated in more than half of human cancers and the compound methylene quinuclidinone (MQ) was shown to reactivate p53 mutants by binding covalently to cysteine residues. Here, the authors present crystal structures of wild-type and cancer related p53 mutant core domains bound to MQ alone and in complex with their DNA response elements and observe that MQ is bound to several cysteine residues located at the surface of the core domain.
format	article
author	Oksana Degtjarik Dmitrij Golovenko Yael Diskin-Posner Lars Abrahmsén Haim Rozenberg Zippora Shakked
author_facet	Oksana Degtjarik Dmitrij Golovenko Yael Diskin-Posner Lars Abrahmsén Haim Rozenberg Zippora Shakked
author_sort	Oksana Degtjarik
title	Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)
title_short	Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)
title_full	Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)
title_fullStr	Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)
title_full_unstemmed	Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)
title_sort	structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (mq)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/61ab66026ad342f6901e1b078e2ffc95
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Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)

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