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Tumor Biology
Published in: Tumor Biology 11/2016

01-11-2016 | Original Article

Impact of point mutation P29S in RAC1 on tumorigenesis

Authors: Vidya Rajendran, Chandrasekhar Gopalakrishnan, Rituraj Purohit

Published in: Tumor Biology | Issue 11/2016

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Abstract

A point mutation (P29S) in the RAS-related C3 botulinum toxin substrate 1 (RAC1) was considered to be a trigger for melanoma, a form of skin cancer with highest mortality rate. In this study, we have investigated the pathogenic role of P29S based on the conformational behavior of RAC1 protein toward guanosine triphosphate (GTP). Molecular interaction, molecular dynamics trajectory analysis (RMSD, RMSF, Rg, SASA, DSSP, and PCA), and shape analysis of binding pocket were performed to analyze the interaction energy and the dynamic behavior of native and mutant RAC1 at the atomic level. Due to this mutation, the RAC1 switch I region acquired more flexibility and, to compensate it, the switch II region becomes rigid in their conformational space, as a result of which the interaction energy of the protein for GTP increased. The overall results strongly implied that the changes in atomic conformation of the switch I and II regions in mutant RAC1 protein were a significant reason for its malignant transformation and tumorigenesis. We raised the opportunity for researchers to design possible therapeutic molecule by considering our findings.
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Metadata
Title
Impact of point mutation P29S in RAC1 on tumorigenesis
Authors
Vidya Rajendran
Chandrasekhar Gopalakrishnan
Rituraj Purohit
Publication date
01-11-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5329-y

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