Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.

PIM1, is a serine/threonine proto-oncogene kinase, involved in many biological functions, including cell survival, proliferation, and differentiation, thus play a key role in oncogenesis. It plays a crucial role in the onset and progression of various hematopoietic and non-hematopoietic malignancies...

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Autores principales:	Alaa Shafie, Shama Khan, Sagar Batra, Farah Anjum, Taj Mohammad, Shoaib Alam, Dharmendra Kumar Yadav, Asimul Islam, Md Imtaiyaz Hassan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/20ea66356c824631b95621659e698cf5
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spelling	oai:doaj.org-article:20ea66356c824631b95621659e698cf52021-12-02T20:13:35ZInvestigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.1932-620310.1371/journal.pone.0258929https://doaj.org/article/20ea66356c824631b95621659e698cf52021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258929https://doaj.org/toc/1932-6203PIM1, is a serine/threonine proto-oncogene kinase, involved in many biological functions, including cell survival, proliferation, and differentiation, thus play a key role in oncogenesis. It plays a crucial role in the onset and progression of various hematopoietic and non-hematopoietic malignancies, including acute myeloid leukemia and prostate cancer. Mutations in PIM1, especially in its kinase domain, can induce abnormal structural changes and thus alter functionalities that can lead to disease progression and other complexities. Herein, we have performed an extensive analysis of the PIM1 mutations at sequence and structure level while utilizing state-of-the-art computational approaches. Based on the impact on PIM1, numerous pathogenic and destabilizing mutations were identified and subsequently analyzed in detail. Finally, two amino acid substitutions (W109C and F147C) in the kinase domain of PIM1 were selected to explore their impact on the PIM1 structure in a time evolution manner using all-atom molecular dynamics (MD) simulations for 200 ns. MD results indicate significant conformational altercations in the structure of PIM1, especially upon F147C mutation. This study provides a significant insight into the PIM1 dysfunction upon single amino acid substitutions, which can be utilized to get insights into the molecular basis of PIM1-associated disease progression.Alaa ShafieShama KhanSagar BatraFarah AnjumTaj MohammadShoaib AlamDharmendra Kumar YadavAsimul IslamMd Imtaiyaz HassanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258929 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alaa Shafie Shama Khan Sagar Batra Farah Anjum Taj Mohammad Shoaib Alam Dharmendra Kumar Yadav Asimul Islam Md Imtaiyaz Hassan Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.
description	PIM1, is a serine/threonine proto-oncogene kinase, involved in many biological functions, including cell survival, proliferation, and differentiation, thus play a key role in oncogenesis. It plays a crucial role in the onset and progression of various hematopoietic and non-hematopoietic malignancies, including acute myeloid leukemia and prostate cancer. Mutations in PIM1, especially in its kinase domain, can induce abnormal structural changes and thus alter functionalities that can lead to disease progression and other complexities. Herein, we have performed an extensive analysis of the PIM1 mutations at sequence and structure level while utilizing state-of-the-art computational approaches. Based on the impact on PIM1, numerous pathogenic and destabilizing mutations were identified and subsequently analyzed in detail. Finally, two amino acid substitutions (W109C and F147C) in the kinase domain of PIM1 were selected to explore their impact on the PIM1 structure in a time evolution manner using all-atom molecular dynamics (MD) simulations for 200 ns. MD results indicate significant conformational altercations in the structure of PIM1, especially upon F147C mutation. This study provides a significant insight into the PIM1 dysfunction upon single amino acid substitutions, which can be utilized to get insights into the molecular basis of PIM1-associated disease progression.
format	article
author	Alaa Shafie Shama Khan Sagar Batra Farah Anjum Taj Mohammad Shoaib Alam Dharmendra Kumar Yadav Asimul Islam Md Imtaiyaz Hassan
author_facet	Alaa Shafie Shama Khan Sagar Batra Farah Anjum Taj Mohammad Shoaib Alam Dharmendra Kumar Yadav Asimul Islam Md Imtaiyaz Hassan
author_sort	Alaa Shafie
title	Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.
title_short	Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.
title_full	Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.
title_fullStr	Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.
title_full_unstemmed	Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.
title_sort	investigating single amino acid substitutions in pim1 kinase: a structural genomics approach.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/20ea66356c824631b95621659e698cf5
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Investigating single amino acid substitutions in PIM1 kinase: A structural genomics approach.

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