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1.
Ramireddy Eswarayya Nelissen Hilde Leuendorf Jan Erik Van Lijsebettens Mieke Inzé Dirk Schmülling Thomas 《Plant molecular biology》2021,106(6):555-567
Plant Molecular Biology - Root-specific expression of a cytokinin-degrading CKX gene in maize roots causes formation of a larger root system leading to higher element content in shoot organs. The... 相似文献
2.
Parasuraman Aiya Subramani Venkata Ramireddy Narala R Dinakaran Michael Dakshayani Lomada Madhava C Reddy 《Bioinformation》2015,11(5):248-253
Protein prenylation is a posttranslational modification that is indispensable for translocation of membrane GTPases like Ras, Rho,
Ras etc. Proteins of Ras family undergo farnesylation by FTase while Rho family goes through geranylgeranylation by GGTase1.
There is only an infinitesimal difference in signal recognition between FTase and GGTase1. FTase inhibitors mostly end up
selecting the cells with mutated Ras proteins that have acquired affinity towards GGTase1 in cancer microcosms. Therefore, it is of
interest to identify GGTase1 and FTase dual inhibitors using the docking tool AutoDock Vina. Docking data show that curcumin
(from turmeric) has higher binding affinity to GGTase1 than that of established peptidomimetic GGTase1 inhibitors (GGTI) such as
GGTI-297, GGTI-298, CHEMBL525185. Curcumin also interacts with FTase with binding energy comparable to co-crystalized
compound 2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-[1-amino-1-(1-methyl-1h-imidizol-5-yl)-ethyl]-benzonitrile (BNE).
The docked complex was further simulated for 10 ns using molecular dynamics simulation for stability. Thus, the molecular basis
for curcumin binding to GGTase1 and FTase is reported. 相似文献
3.
A. Desai K. Murali-Krishna B. Ramireddy V. Ravi R. Manjunath 《Journal of biosciences》1997,22(1):33-45
Japanese encephalitis virus (JEV) is a positive stranded RNA virus that belongs to the flavivirus group. JEV infection damages
the central nervous system (CNS) and is one of the main causative agents of acute encephalitis. H-2 restricted virus-specific
cytotoxic T lymphocytes (CTL) have been generated specifically against JEV in our laboratory and these CTL have been shown
to protect mice against lethal challenge with JEV. Virus replication was found to be inhibited in the brains of animals that
were adoptively transferred with JEV specific CTL as revealed by immunohistological staining as well as viral plaque assays.
We further show that virus specific CTL could be recovered from such protected mice as long as 45 days after adoptive transfer. 相似文献
4.
Anil Gudipudi Chitra Bajji Ravikanth Reddy Kosana Kalpana Panati Dakshayani Lomada Venkat R. R. Arva Tatireddigari Venkata Ramireddy Narala 《Biotechnology letters》2014,36(9):1761-1769
Fuzeon (Enfuvirtide, T20) is the first fusion inhibitor approved by the FDA of the USA for the treatment of HIV/AIDS in combination with other anti-retroviral drugs. Enfuvirtide is a synthetic peptide that blocks the entry of HIV into healthy host CD4 cells, which requires very high (90 mg twice daily) therapeutic doses. To increase the yield of Enfuvirtide, a gene polymerization strategy was introduced and recombinant T20 (rT20) was expressed in Escherichia coli as a five copy repeat polypeptide with a histidine-tag. The five copy rT20 was purified by Ni-affinity chromatography and cleaved to single rT20 units by cyanogen bromide. Finally, single rT20 units were purified by reversed phase chromatography giving a yield (400 mg/l) with a purity >95 %, which exhibited specific biological activity similar to Fuzeon. 相似文献
5.
6.
Kaja Murali-Krishna Bommireddy Ramireddy Vasanthapuram Ravi Ramanathapuram Manjunath 《Microbiology and immunology》1995,39(12):1021-1024
We have previously reported that Lyt2+ cytotoxic T lymphocytes (CTL) can be raised against Japanese encephalitis virus (JEV) in BALB/c mice. In order to confirm the presence of H-2Kd-restricted CTL and to examine their cross-recognition of West Nile virus (WNV), we tested the capacity of anti-JEV CTL to lyse uninfected syngeneic target cells that were pulsed with synthetic peptides. The sequence of the synthetic peptides was predicted based upon the H-2Kd binding consensus motif. We show here that preincubation of uninfected syngeneic targets (P388D1) with JEV NS1- and NS3-derived peptides [NS1 (891-899) and NS3 (1804-1812)], but not with JEV NS5-derived peptide [NS5 (3370-3378)], partially sensitized them for lysis by polyclonal anti-JEV CTL. These results indicate the CTL recognition of NS1- and NS3-derived peptides of JEV. 相似文献
7.
Bommireddy R Engle SJ Ormsby I Boivin GP Babcock GF Doetschman T 《Cellular immunology》2004,232(1-2):96-104
Transforming growth factor beta1 (TGFbeta1) is a potent negative immunoregulatory molecule. We have previously shown that the autoimmune-mediated weaning-age lethality of Tgfb1-/- mice is reversed upon genetic combination with Scid or Rag null alleles. Here, we show that elimination of T but not B cells is sufficient for the reversal, but elimination of either CD4+ or CD8+ cells is not. Although elimination of B cells does not rescue TGFbeta1-deficient animals from autoimmunity, B cells are hyperresponsive to LPS in the absence of TGFbeta1. TGFbeta1 deficiency leads to activation of CD8+ T cells as suggested by down-modulation of CD8 even in the absence of CD4+ T cells. This study provides evidence that both CD4+ and CD8+ T cells, but not B cells, have the ability to cause inflammation in the absence of TGFbeta1. However, though TGFbeta1-deficient B cells are hyperresponsive to stimulation, alone they are not sufficient to cause inflammation. 相似文献
8.
Mohamad Azhar Moying Yin Ramireddy Bommireddy John J. Duffy Junqi Yang Sharon A. Pawlowski Gregory P Boivin Sandra J. Engle L.P. Sanford Christina Grisham Ram R. Singh George F. Babcock Thomas Doetschman 《Genesis (New York, N.Y. : 2000)》2009,47(6):423-431
Transforming growth factor β1 (TGFβ1) is a multifunctional growth factor involved in wound healing, tissue fibrosis, and in the pathogenesis of many syndromic diseases (e.g., Marfan syndrome, Camurati‐Engelmann disease) and muscular, neurological, ophthalmic, cardiovascular and immunological disorders, and cancer. Since the generation of Tgfb1 knockout mice, there has been extraordinary progress in understanding its physiological and pathophysiological function. Here, we report the generation of a conditional knockout allele for Tgfb1 in which its exon 6 is flanked with LoxP sites. As proof of principle, we crossed these mice to LckCre transgenic mice and specifically disrupted Tgfb1 in T cells. The results indicate that T‐cell‐produced TGFβ1 is required for normal in vivo regulation of peripheral T‐cell activation, maintenance of T‐cell homeostasis, and suppression of autoimmunity. genesis 47:423–431, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
9.
Mallikarjuna Thippanna Parasuraman Aiya Subramani Dakshayani Lomada Venkata Ramireddy Narala Madhava C Reddy 《Bioinformation》2013,9(19):973-977
Protein prenylation is a post translational modification that is indispensable for Ras–Rho mediated tumorigenesis. In mammals,
three enzymes namely protein farnesyltransferase (FTase), geranylgeranyl transferase1 (GGTase1), and geranylgeranyl transferase2
(GGTase2) were found to be involved in this process. Usually proteins of Ras family will be farnesylated by FTase, Rho family will
be geranylgeranylated by GGTase1. GGTase2 is exclusive for geranylgeranylating Rab protein family. FTase inhibitors such as FTI-
277 are potent anti-cancer agents in vitro. In vivo, mutated Ras proteins can either improve their affinity for FTase active site or
undergo geranylgeranylation which confers resistance and no activity of FTase inhibitors. This led to the development of GGTase1
inhibitors. A well-defined 3-D structure of human GGTase1 protein is lacking which impairs its in silico and rational designing of
inhibitors. A 3-D structure of human GGTase1 was constructed based on primary sequence available and homology modeling to
which pubchem molecules library was virtually screened through AutoDock Vina. Our studies show that natural compounds
Camptothecin (-8.2 Kcal/mol), Curcumin (-7.3 Kcal/mol) have higher binding affinities to GGTase-1 than that of established
peptidomimetic GGTase-1 inhibitors such as GGTI-297 (-7.5 Kcal/mol), GGTI-298 (-7.5 Kcal/mol), CHEMBL525185 (-7.2
Kcal/mol). 相似文献
10.
Saxena V Lienesch DW Zhou M Bommireddy R Azhar M Doetschman T Singh RR 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(3):1903-1912
Ample evidence suggests a role of TGF-beta in preventing autoimmunity. Multiorgan inflammatory disease, spontaneous activation of self-reactive T cells, and autoantibody production are hallmarks of autoimmune diseases, such as lupus. These features are reminiscent of the immunopathology manifest in TGF-beta1-deficient mice. In this study, we show that lupus-prone (New Zealand Black and White)F(1) mice have reduced expression of TGF-beta1 in lymphoid tissues, and TGF-beta1 or TGF-beta1-producing T cells suppress autoantibody production. In contrast, the expression of TGF-beta1 protein and mRNA and TGF-beta signaling proteins (TGF-beta receptor type II and phosphorylated SMAD3) increases in the target organs, i.e., kidneys, of these mice as they age and develop progressive organ damage. In fact, the levels of TGF-beta1 in kidney tissue and urine correlate with the extent of chronic lesions that represent local tissue fibrosis. In vivo TGF-beta blockade by treatment of these mice with an anti-TGF-beta Ab selectively inhibits chronic fibrotic lesions without affecting autoantibody production and the inflammatory component of tissue injury. Thus, TGF-beta plays a dual, seemingly paradoxical, role in the development of organ damage in multiorgan autoimmune diseases. According to our working model, reduced TGF-beta in immune cells predisposes to immune dysregulation and autoantibody production, which causes tissue inflammation that triggers the production of anti-inflammatory cytokines such as TGF-beta in target organs to counter inflammation. Enhanced TGF-beta in target organs, in turn, can lead to dysregulated tissue repair, progressive fibrogenesis, and eventual end-organ damage. 相似文献