Deciphering the impact of missense mutations on structure and dynamics of SMAD4 protein involved in pathogenesis of gall bladder cancer.

Journal of Biomolecular Structure & Dynamics
Rakesh KumarShowket Hussain

Abstract

Gall bladder cancer (GBC) is the most common malignancy of biliary tract cancer associated with high mortality rate and poor prognosis due to lack of suitable biomarkers. In this study, we explored the structural and functional effects of different missense mutations occurs in SMAD4 that was associated with the development of GBC. We utilized in silico methods to predict the harmful effects of nonsynonymous missense mutations and monitored the stability of protein. We found that all mutations (D351N, G352E, R361C, R361H, E526Q) associated with SMAD4 were deleterious in nature resulting in the formation of deformed or unstable protein structure. Molecular dynamics simulation studies revealed how these mutations affect protein stability, structure, conformation and function. We observed, different mutants increase the compactness and rigidity of SMAD4 protein, alter secondary structure composition, decrease the surface area and protein-ligand interaction and affect its conformation. Findings of current work indicated that the analyzed mutations might affect the structure of protein and its caliber to interact with other molecules, which probably related to functional impairment of SMAD4 upon D351N, G352E, R361C, R361H, E526Q muta...Continue Reading

References

Mar 5, 1992·Nature·R LüthyD Eisenberg
Aug 1, 1995·Current Opinion in Biotechnology·A Sali
Dec 1, 1993·Proteins·A AmadeiH J Berendsen
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
May 5, 2001·Genome Research·P C Ng, S Henikoff
Apr 5, 2002·Protein Engineering·Mariël G PikkemaatDick B Janssen
Dec 19, 2003·Nucleic Acids Research·Rolf ApweilerLai-Su L Yeh
Jan 12, 2005·Structure·Debnath Pal, David Eisenberg
Jun 28, 2005·Nucleic Acids Research·Emidio CapriottiRita Casadio
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Apr 18, 2006·Structure·Raik GrünbergJohan Leckner
May 23, 2007·Nucleic Acids Research·Markus Wiederstein, Manfred J Sippl
May 29, 2007·Nucleic Acids Research·Yana Bromberg, Burkhard Rost
Oct 13, 2007·Proteins·Pascal BenkertDietmar Schomburg
Jan 25, 2008·BMC Bioinformatics·Yang Zhang
Feb 1, 2008·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Maria Stepanova
Feb 17, 2009·Seminars in Oncology Nursing·Kathleen K Reed, Rita Wickham
Mar 18, 2009·Biophysical Journal·Oznur TastanHagai Meirovitch
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Nov 1, 2011·BMC Biology·Jacob D Durrant, J Andrew McCammon
Dec 5, 2012·Cancer Discovery·Jennifer N Wu, Charles W M Roberts
Nov 22, 2013·Journal of the Royal Society, Interface·Sree V ChintapalliChristopher A Reynolds
Jan 24, 2014·PLoS Computational Biology·Jaroslav BendlJiri Damborsky
Mar 19, 2014·Clinical Epidemiology·Rajveer Hundal, Eldon A Shaffer
Jun 16, 2015·Frontiers in Molecular Biosciences·Pierrick CraveurAlexandre G de Brevern
Feb 10, 2016·Cancer Metastasis Reviews·Jason K SicklickRazelle Kurzrock
May 6, 2016·Annual Review of Biochemistry·Andreas C Joerger, Alan R Fersht
Jul 19, 2017·Trends in Cancer·Selcuk Colak, Peter Ten Dijke
Jan 24, 2018·Journal of Hepatology·Christopher P WardellHidewaki Nakagawa
Apr 18, 2018·Journal of Biomolecular Structure & Dynamics·Iris Nira SmithCharis Eng
Nov 21, 2018·Mutation Research. Reviews in Mutation Research·Ravi MehrotraG K Rath

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.