In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 10 ( 2021-10-22), p. e0258929-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0258929
DOI:
10.1371/journal.pone.0258929.g001
DOI:
10.1371/journal.pone.0258929.g002
DOI:
10.1371/journal.pone.0258929.g003
DOI:
10.1371/journal.pone.0258929.g004
DOI:
10.1371/journal.pone.0258929.g005
DOI:
10.1371/journal.pone.0258929.g006
DOI:
10.1371/journal.pone.0258929.g007
DOI:
10.1371/journal.pone.0258929.g008
DOI:
10.1371/journal.pone.0258929.g009
DOI:
10.1371/journal.pone.0258929.s001
DOI:
10.1371/journal.pone.0258929.s002
DOI:
10.1371/journal.pone.0258929.s003
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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