The dynamic conformational landscape of the protein methyltransferase SETD8

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Autor(es): dc.creatorShi Chen-
Autor(es): dc.creatorWiewiora, Rafal P.-
Autor(es): dc.creatorFanwang Meng-
Autor(es): dc.creatorBabault, Nicolas-
Autor(es): dc.creatorAnqi Ma-
Autor(es): dc.creatorWenyu Yu-
Autor(es): dc.creatorKun Qian-
Autor(es): dc.creatorHao Hu-
Autor(es): dc.creatorHua Zou-
Autor(es): dc.creatorJunyi Wang-
Autor(es): dc.creatorShijie Fan-
Autor(es): dc.creatorBlum, Gil-
Autor(es): dc.creatorPittella-Silva, Fabio-
Autor(es): dc.creatorBeauchamp, Kyle A.-
Autor(es): dc.creatorTempel, Wolfram-
Autor(es): dc.creatorHualiang Jiang-
Autor(es): dc.creatorKaixian Chen-
Autor(es): dc.creatorSkene, Robert J.-
Autor(es): dc.creatorYujun George Zheng-
Autor(es): dc.creatorBrown, Peter J.-
Autor(es): dc.creatorJian Jin Cheng Luo-
Autor(es): dc.creatorChodera, John D.-
Autor(es): dc.creatorMinkui Luo-
Data de aceite: dc.date.accessioned2024-10-23T15:38:31Z-
Data de disponibilização: dc.date.available2024-10-23T15:38:31Z-
Data de envio: dc.date.issued2022-09-05-
Data de envio: dc.date.issued2022-09-05-
Data de envio: dc.date.issued2019-05-13-
Fonte completa do material: dc.identifierhttps://repositorio.unb.br/handle/10482/44692-
Fonte completa do material: dc.identifierhttps://doi.org/10.7554/eLife.45403-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/888190-
Descrição: dc.descriptionElucidating the conformational heterogeneity of proteins is essential for understanding protein function and developing exogenous ligands. With the rapid development of experimental and computational methods, it is of great interest to integrate these approaches to illuminate the conformational landscapes of target proteins. SETD8 is a protein lysine methyltransferase (PKMT), which functions in vivo via the methylation of histone and nonhistone targets. Utilizing covalent inhibitors and depleting native ligands to trap hidden conformational states, we obtained diverse X-ray structures of SETD8. These structures were used to seed distributed atomistic molecular dynamics simulations that generated a total of six milliseconds of trajectory data. Markov state models, built via an automated machine learning approach and corroborated experimentally, reveal how slow conformational motions and conformational states are relevant to catalysis. These findings provide molecular insight on enzymatic catalysis and allosteric mechanisms of a PKMT via its detailed conformational landscape.-
Formato: dc.formatapplication/pdf-
Publicador: dc.publishereLife Sciences Publications Ltd.-
Direitos: dc.rightsAcesso Aberto-
Direitos: dc.rightsCopyright Chen et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.-
Palavras-chave: dc.subjectProteínas-
Palavras-chave: dc.subjectCâncer-
Título: dc.titleThe dynamic conformational landscape of the protein methyltransferase SETD8-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional – UNB

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