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In-silico and in-vitro investigation of STAT3-PIM1 heterodimeric complex: Its mechanism and inhibition by curcumin for cancer therapeutics

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Title In-silico and in-vitro investigation of STAT3-PIM1 heterodimeric complex: Its mechanism and inhibition by curcumin for cancer therapeutics
Not Available
 
Creator Sutapa Mahata
Santosh Kumar Behera
Sunil Kumar
Pranab Kumar Sahoo
Sinjini Sarkar
Mobashar Hussain Urf Turabe Fazil
Vilas D. Nasare
 
Subject Molecular docking
Molecular dynamics simulations
STAT3
PIM1
Curcumin
Cancer
 
Description Not Available
The functional activity among STAT3 and PIM1, are key signaling events for cancer cell function. Curcumin, a
diarylheptanoid isolated from turmeric, effectively inhibits STAT3 signaling. Selectively, we attempted to
address interactions of STAT3, PIM1 and Curcumin for therapeutic intervention using in silico and in vitro
experimental approaches. Firstly, protein-protein interactions (PPI) between STAT3-PIM1 by molecular docking
studies reflected salt bridges among Arg279 (STAT3)-Glu140 (PIM1) and Arg282 (STAT3)-Asp100 (PIM1), with a binding affinity of − 38.6 kcal/mol. Secondly, molecular dynamics simulations of heterodimeric STAT3-PIM1
complex with curcumin revealed binding of curcumin on PIM-1 interface of the complex through hydrogen
bonds (Asp155) and hydrophobic interactions (Leu13, Phe18, Val21, etc.) with a binding energy of − 7.3 kcal/
mol. These PPIs were confirmed in vitro by immunoprecipitation assays in MDA-MB-231 cells. Corroborating our results, expression levels of STAT3 and PIM1 decreased after curcumin treatment. We observed that PIM1 in teracts with STAT3 and these functional interactions are disrupted by curcumin. The calculated band energy gap of heterodimeric STAT3-PIM1-Curcumin complex was of 9.621 kcal/mol. The present study revealed the role of curcumin in STAT3/PIM1 signaling and its binding affinity to the complex for design of advanced cancer
therapeutics.
Not Available
 
Date 2022-05-28T09:10:26Z
2022-05-28T09:10:26Z
2022-03-23
 
Type Research Paper
 
Identifier Sutapa Mahata, Santosh Kumar Behera, Sunil Kumar, Pranab Kumar Sahoo, Sinjini Sarkar, Mobashar Hussain Urf Turabe Fazil, Vilas D. Nasare (2022). In-silico and in-vitro investigation of STAT3-PIM1 heterodimeric complex: Its mechanism and inhibition by curcumin for cancer therapeutics, International Journal of Biological Macromolecules, 208, 356-366, https://doi.org/10.1016/j.ijbiomac.2022.03.137.
0141-8130
http://krishi.icar.gov.in/jspui/handle/123456789/72406
 
Language English
 
Relation Not Available;
 
Publisher Elsevier