The 14-3-3ζ protein acts as a molecular switch in regulating the TGF-β pathway, which alters from a tumor suppressor in the early stage of breast cancer to a promoter of metastasis in the late stage.

Sudandira Doss C

Department of Biotechnology

School of Bio Sciences and Technology

Vellore Campus

Kamalesh D.K

Kamalesh, D.

Ramireddy S

Raguraman P.R

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

&nbsp;

&nbsp;

VIT University

Molecular BioSystems

Drugs targeting transcriptional cofactors (TcoFs) function well in mouse models but fail to replicate their efficacy in human beings. Thus, we performed a comparative study on the TcoFs of humans and mice to find the similarity and dissimilarity between them. We observed high similarity in protein sequence and interacting domains between humans and mice. At the same time, dissimilarity was gradually increased in terms of interacting motifs, post-translational modifications, and molecular switches. Indeed, some of the post-translational modifications and molecular switches present in human beings are preferentially exempted in mice. Thus, structure-specific drugs designed to target TcoFs are functional in mice but fail in human beings, because the absence of some molecular switches in mice offers a particular conformation on the interacting motifs, which might facilitate drug binding. But in humans, owing to the presence of molecular switches, drug binding is not possible. From molecular dynamics simulation analysis, we inferred 8 different molecular switches on 3 proteins and found that 5 molecular switches influenced structural change in interacting motifs and revealed the reason for the functioning of drug in mice but not in human beings. From protein interaction network analysis, we find that a few interacting partners in mice are exempted in humans, and in both the cases the interacting partners are high when the domains are highly structured and the interacting partners are low when the domains are highly disordered. Hence, we are sure that our investigations will provide a promising support in future for designing drugs with high translational efficiency from mice models to human clinical trials. © 2018 Wiley Periodicals, Inc.

Journal of Cellular Biochemistry

Comparative analysis of human and mouse transcriptional cofactors (TcoFs) with special emphasis on intrinsically disordered regions and their associated regulating post-translational modifications

Tumor Biology

Impact of point mutation P29S in RAC1 on tumorigenesis

Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led to reduced affinity of the respective enzymes for isocitrate and increased affinity for α-ketoglutarate (AKG) and NADPH.

Structural analysis of oncogenic mutation of isocitrate dehydrogenase 1

Molecular and Cellular Biochemistry

Computational investigation of molecular mechanism and neuropathological implications in Huntington disease

Cell Biochemistry and Biophysics

Computational Screening of Disease-Associated Mutations in OCA2 Gene

Mucin 1 is an important tumor marker, and is notable for the autoproteolytic event, a signature of all SEA domain containing proteins. However the isoform MUC1/Y, unlike its closest counterpart MUC1/X, is noted to be uncleavable despite the presence of the catalytic site. Sequence analysis has revealed the presence of an 18 residue segment spliced out from MUC1/Y marking the only difference between uncleavable MUC1/Y and cleavable MUC1/X mucin 1 isoforms. This work was aimed at studying in silico, the structural and functional significance of the 18 residue insert in the cleavage process. 3-Dimensional structures of the isoforms were predicted using a combined threading and ab initio method followed by mutation and normal mode analysis. Our analysis revealed both isoforms to poses an intact SEA domain, nevertheless, an altered functional scaffold around the cleavage site was noted between the structures. Mutation analysis by alanine substitutions at the insert region revealed Ile67 to be more destabilizing, resulting in increased fluctuation of the neighboring residues. Predicted molecular motions of the protein indicated localized motions in the native, rather than the mutated model. Intramolecular interactions between the native and I67A structures showed wide variations in main chain and side chain interactions. Furthermore, the findings suggest the neighboring residues, in particular Ile67 contribute more to the structural and functional properties of the protein and hence it is predicted to be one of the crucial residues for the cleavable nature of MUC1/X. © 2013 The Royal Society of Chemistry.

Computational investigation of theoretical models of cleavable and uncleavable mucin 1 isoforms

Expediting dynamics approach to understand the influence of 14-3-3ζ causing metastatic cancer through the interaction of YAP1 and β-TRCP

Journal	Data powered by TypesetMolecular BioSystems
Publisher	Data powered by TypesetRoyal Society of Chemistry (RSC)
ISSN	1742-206X
Open Access	0