Structural debilitation of mutation G322D associated with MSH2 and their role in triple negative breast cancer

Journal of Biomolecular Structure & Dynamics
Ramireddy SriroopreddyC Sudandiradoss

Abstract

The missense mutation in the mismatch repair gene MSH2 underlies in several hereditary cancers. In this study, we have detailed the disruptive mutation of G322D that overtly pathogenic and clinically relevant to the triple negative breast cancer (TNBC) on the basis of structural aspect to untangle the unknown factors. We systematically evaluated the conformational changes that undergo upon mutation from the annotation of intra-residual contacts, secondary structural arrangements and fold recognition through molecular dynamics simulation. At first, we interpreted the total of 88 intra-molecular interaction which is required minimally to maintain the native structural architecture. Adequately, the molecular dynamics approach is well contributed toward structural modification that takes places in C-terminal linking 290-294(L20), 339-347(L23-T16- α9-T17) and 373-395(α12-T19-20-L26-T21-L27-T22) in contrast to native 290-294(β8), 339-347(T20-α9-T21-α10), 373-395(α12-T19-20-L26-T21-L27-T22) provides a straightforward evidence that is underpinning destabilization and protein misfolding. Eventually, we have highlighted the structural debilitation of G322D in the core region of 303-309 L23-T18-α6 - L21- α8, and 326-330 α7-T19-L25 -α9 not...Continue Reading

References

Aug 25, 1983·Journal of Molecular Biology·D J Barlow, J M Thornton
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jan 1, 1997·Methods in Enzymology·D EisenbergJ U Bowie
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·J P Gallivan, D A Dougherty
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Dec 28, 1999·Journal of Molecular Biology·D A Debe, W A Goddard
Apr 30, 2003·Protein Science : a Publication of the Protein Society·Björn Wallner, Arne Elofsson
Dec 19, 2003·Nucleic Acids Research·Rolf ApweilerLai-Su L Yeh
Dec 21, 2004·Nucleic Acids Research·Ada HamoshVictor A McKusick
Apr 14, 2006·Nature Reviews. Molecular Cell Biology·Josef Jiricny
Aug 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·H Jane DysonHarold A Scheraga
May 23, 2007·Nucleic Acids Research·Markus Wiederstein, Manfred J Sippl
Jun 23, 2007·Nucleic Acids Research·K G TinaN Srinivasan
Jul 17, 2007·Progress in Biophysics and Molecular Biology·Pinak Chakrabarti, Rajasri Bhattacharyya
Oct 9, 2007·Breast Cancer Research and Treatment·David S P TanJorge S Reis-Filho
Apr 15, 2008·Mechanisms of Ageing and Development·Peggy Hsieh, Kazuhiko Yamane
May 3, 2008·The Breast : Official Journal of the European Society of Mastology·Hakan MersinKaptan Gülben
May 12, 2009·Nucleic Acids Research·Pascal BenkertTorsten Schwede
Jun 19, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A GoldhirschUNKNOWN Panel members
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Jun 12, 2010·Molecular Oncology·Franca PodoUNKNOWN FEMME Consortium
Sep 2, 2010·Breast Cancer Research : BCR·Emad A RakhaIan O Ellis
Oct 12, 2011·Current Opinion in Oncology·Sheeba IrshadAndrew Tutt
Jan 20, 2012·Nature·Christopher J Lord, Alan Ashworth
Sep 21, 2012·The American Journal of Surgical Pathology·Yong H WenJinru Shia
Sep 26, 2013·Methods in Molecular Biology·Charles C David, Donald J Jacobs
Nov 16, 2013·Nucleic Acids Research·Melissa J LandrumDonna R Maglott
May 1, 2016·Nucleic Acids Research·Debswapna BhattacharyaJianlin Cheng
Jan 14, 2018·International Journal of Cancer. Journal International Du Cancer·Esther M JohnAnna H Wu
Jan 19, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Maegan E RobertsWendy K Chung
Jan 25, 2018·Journal of Biomolecular Structure & Dynamics·Mahboubeh ZareiYounes Ghasemi

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Citations

Apr 21, 2020·Journal of Biomolecular Structure & Dynamics·Subramanian BoopathiPonmalai Kolandaivel
Feb 29, 2020·Journal of Biomolecular Structure & Dynamics·Parth Sarthi Sen GuptaAmal Kumar Bandyopadhyay

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Methods Mentioned

BETA
MDS
MDSs
PCA
protein folding

Software Mentioned

ProQ
Discovery Studio
MolProbity
SWISS
PROCHECK
GROMACS
mean
PIC
SwissPdb Viewer ( SPDBV )
VMD

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