02237nas a2200241   4500008004100000022001400041245011700055210006900172260000800241520140600249653002001655653001701675653001801692653001901710653001301729100002101742700002201763700001701785700002001802700001801822700002401840856013101864       2019                        eng d  a0887-358500aIn vitro and in silico studies on membrane interactions of diverse Capsicum annuum flower gamma-thionin peptides0 aIn vitro and in silico studies on membrane interactions of diver  cAUG3 a<p>Thionins are small, cysteine-rich peptides that play an important role in plant defense, primarily through their interactions with membranes. Eight novel gamma-thionin peptides (CanThio1-8) were isolated from the flower of Capsicum annuum. Sequence analysis revealed that the peptides cluster into three groups. A representative peptide from each group (CanThio1, 2, and 3) was used for experimental characterization. Interestingly, peptides were found to possess some cytotoxic activity against normal human embryonic kidney cell line but higher cytotoxicity against cancer cell line MCF-7. CanThio3 peptide was chosen as a representative peptide to study the molecular mechanism of action on membranes. Microsecond timescale atomistic simulations of CanThio3 were performed in the presence of a POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) lipid bilayer. Simulations revealed that CanThio3 interacts with the bilayer and causes lipid thinning in the vicinity. Nonpolar amino acids specific to the alpha-core region of CanThio3 along with nonpolar residues in the gamma-core region are seen to interact with the lipid tails. The differences in the amino acid sequence of CanThio peptides in these regions explain the variability in cytotoxic activities. In summary, our results demonstrate the membrane-mediated activity of a novel series of gamma-thionin peptides from C. annuum.</p>
10aCapsicum annuum10aCytotoxicity10agamma-thionin10aMD simulations10aMembrane1 aNikte, Siddhanta1 aGahankari, Apurva1 aMulla, Javed1 aSengupta, Durba1 aJoshi, Manali1 aTamhane, Vaijayanti  uhttps://library.ncl.res.in/content/vitro-and-silico-studies-membrane-interactions-diverse-capsicum-annuum-flower-gamma-thionin02060nas a2200169   4500008004100000020001800041245011900059210006900178260000800247300001200255490000800267520142900275100001801704700002101722700002001743856012701763       2022                        eng d  a978032398895700aMolecular determinants of GPCR pharmacogenetics: deconstructing the population variants in β2-adrenergic receptor0 aMolecular determinants of GPCR pharmacogenetics deconstructing t  cJAN  a361-3960 v1283 a<p>G protein-coupled receptors (GPCRs) are membrane proteins that play a central role in cell signaling and constitute one of the largest classes of drug targets. The molecular mechanisms underlying GPCR function have been characterized by several experimental and computational methods and provide an understanding of their role in physiology and disease. Population variants arising from nsSNPs affect the native function of GPCRs and have been implicated in differential drug response. In this chapter, we provide an overview on GPCR structure and activation, with a special focus on the β2-adrenergic receptor (β2-AR). First, we discuss the current understanding of the structural and dynamic features of the wildtype receptor. Subsequently, the population variants identified in this receptor from clinical and large-scale genomic studies are described. We show how computational approaches such as bioinformatics tools and molecular dynamics simulations can be used to characterize the variant receptors in comparison to the wildtype receptor. In particular, we discuss three examples of clinically important variants and discuss how the structure and function of these variants differ from the wildtype receptor at a molecular level. Overall, the chapter provides an overview of structure and function of GPCR variants and is a step towards the study of inter-individual differences and personalized medicine.</p>
1 aJoshi, Manali1 aNikte, Siddhanta1 aSengupta, Durba  uhttps://library.ncl.res.in/content/molecular-determinants-gpcr-pharmacogenetics-deconstructing-population-variants-%CE%B22