Browsing by Author "Prajapati, K.S"

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    Emerging role of ZBTB7A as an oncogenic driver and transcriptional repressor
    (Elsevier, 2020) Gupta, S; Singh, A.K; Prajapati, K.S; Kushwaha, P.P; Shuaib, M; Kumar, S.
    ZBTB7A is a member of the POK family of transcription factors that possesses a POZ-domain at the N-terminus and Krüppel-like zinc-finger at the c-terminus. ZBTB7A was initially isolated as a protein that binds to the inducer of the short transcript of HIV-1 virus TAT gene promoter. The protein forms a homodimer through protein-protein interaction via the N-terminus POZ-domains. ZBTB7A typically binds to the DNA elements through its zinc-finger domains and represses transcription both by modification of the chromatin organization and through the direct recruitment of transcription factors to gene regulatory regions. ZBTB7A is involved in several fundamental biological processes including cell proliferation, differentiation, and development. It also participates in hematopoiesis, adipogenesis, chondrogenesis, cellular metabolism and alternative splicing of BCLXL, DNA repair, development of oligodendrocytes, osteoclast and unfolded protein response. Aberrant ZBTB7A expression promotes oncogenic transformation and tumor progression, but also maintains a tumor suppressive role depending on the type and genetic context of cancer. In this comprehensive review we provide information about the structure, function, targets, and regulators of ZBTB7A and its role as an oncogenic driver and transcriptional repressor in various human diseases. - 2020 Elsevier B.V.
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    Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies
    (Taylor and Francis Ltd., 2020) Gupta, S; Singh, A.K; Kushwaha, P.P; Prajapati, K.S; Shuaib, M; Senapati, S; Kumar, S.
    Coronaviruses are contagious pathogens primarily responsible for respiratory and intestinal infections. Research efforts to develop antiviral agents against coronavirus demonstrated the main protease (Mpro) protein may represent effective drug target. X-ray crystallographic structure of the SARS-CoV2 Mpro protein demonstrated the significance of Glu166, Cys141, and His41 residues involved in protein dimerization and its catalytic function. We performed in silico screening of compounds from Curcuma longa L. (Zingiberaceae family) against Mpro protein inhibition. Employing a combination of molecular docking, scoring functions, and molecular dynamics simulations, 267 compounds were screened by docking on Mpro crystallographic structure. Docking score and interaction profile analysis exhibited strong binding on the Mpro catalytic domain with compounds C1 (1E,6E)-1,2,6,7-tetrahydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) and C2 (4Z,6E)?1,5?dihydroxy?1,7?bis(4?hydroxyphenyl)hepta?4,6?dien?3?one as lead agents. Compound C1 and C2 showed minimum binding score (�9.08 and �8.07 kcal/mole) against Mpro protein in comparison to shikonin and lopinavir (? ?5.4 kcal/mole) a standard Mpro inhibitor. Furthermore, principal component analysis, free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalytic core of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class. Taken together, this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus. Communicated by Ramaswamy H. Sarma. � 2020, � 2020 Informa UK Limited, trading as Taylor & Francis Group.