Srinivasan M

References (3)

Title : Human alpha beta hydrolase domain containing protein 11 and its yeast homolog are lipid hydrolases - Arya_2017_Biochem.Biophys.Res.Commun_487_875
Author(s) : Arya M , Srinivasan M , Rajasekharan R
Ref : Biochemical & Biophysical Research Communications , 487 :875 , 2017
Abstract : Mammalian alpha/beta hydrolase domain (ABHD) family of proteins have emerged as key regulators of lipid metabolism and are found to be associated with human diseases. Human alpha/beta-hydrolase domain containing protein 11 (ABHD11) has recently been predicted as a potential biomarker for human lung adenocarcinoma. In silico analyses of the ABHD11 protein sequence revealed the presence of a conserved lipase motif GXSXG. However, the role of ABHD11 in lipid metabolism is not known. To understand the biological function of ABHD11, we heterologously expressed the human ABHD11 in budding yeast, Saccharomyces cerevisiae. In vivo [14C]acetate labeling of cellular lipids in yeast cells overexpressing ABHD11 showed a decrease in triacylglycerol content. Overexpression of ABHD11 also alters the molecular species of triacylglycerol in yeast. Similar activity was observed in its yeast homolog, Ygr031w. The role of the conserved lipase motif in the hydrolase activity was proven by the mutation of all conserved amino acid residues of GXSXG motif. Collectively, our results demonstrate that human ABHD11 and its yeast homolog YGR031W have a pivotal role in the lipid metabolism.
ESTHER : Arya_2017_Biochem.Biophys.Res.Commun_487_875
PubMedSearch : Arya_2017_Biochem.Biophys.Res.Commun_487_875
PubMedID: 28465236
Gene_locus related to this paper: human-ABHD11

Title : Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug conjugate, in preclinical animal species and prediction of its pharmacokinetics in humans - Wang_2016_Biopharm.Drug.Dispos_37_93
Author(s) : Wang H , Rangan VS , Sung MC , Passmore D , Kempe T , Wang X , Thevanayagam L , Pan C , Rao C , Srinivasan M , Zhang Q , Gangwar S , Deshpande S , Cardarelli P , Marathe P , Yang Z
Ref : Biopharmaceutics & Drug Disposition , 37 :93 , 2016
Abstract : CD70 is a tumor necrosis factor (TNF)-like type II integral membrane protein that is transiently expressed on activated T- and B-lymphocytes. Aberrant expression of CD70 was identified in both solid tumors and haematologic malignancies. BMS-936561 (alphaCD70_MED-A) is an antibody-drug conjugate composed of a fully human anti-CD70 monoclonal antibody (alphaCD70) conjugated with a duocarmycin derivative, MED-A, through a maleimide-containing citrulline-valine dipeptide linker. MED-A is a carbamate prodrug that is activated by carboxylesterase to its active form, MED-B, to exert its DNA alkylation activity. In vitro serum stability studies suggested the efficiencies of hydrolyzing the carbamate-protecting group in alphaCD70_MED-A followed a rank order of mouse > rat > > monkey > dog ~ human. Pharmacokinetics of alphaCD70_MED-A was evaluated in mice, monkeys, and dogs after single intravenous doses. In mice, alphaCD70_MED-A was cleared rapidly, with no detectable exposures after 15 min following dosing. In contrast, alphaCD70_MED-A was much more stable in monkeys and dogs. The clearance of alphaCD70_MED-A in monkeys was 58 mL/d/kg, ~2-fold faster than that in dogs (31 mL/d/kg). The human PK profiles of the total alphaCD70 and alphaCD70_MED-A were predicted using allometrically scaled monkeys PK parameters of alphaCD70 and the carbamate hydrolysis rate constant estimated in dogs. Comparing the predicted and observed human PK from the phase I study, the dose-normalized concentration-time profiles of alphaCD70_MED-A and the total alphaCD70 were largely within the 5(th) -95(th) percentile of the predicted profiles. Copyright (c) 2015 John Wiley & Sons, Ltd.
ESTHER : Wang_2016_Biopharm.Drug.Dispos_37_93
PubMedSearch : Wang_2016_Biopharm.Drug.Dispos_37_93
PubMedID: 25869904

Title : ROG1 encodes a monoacylglycerol lipase in Saccharomyces cerevisiae - Vishnu_2015_FEBS.Lett_589_23
Author(s) : Vishnu Varthini L , Selvaraju K , Srinivasan M , Nachiappan V
Ref : FEBS Letters , 589 :23 , 2015
Abstract : Lipid metabolism is extensively studied in Saccharomyces cerevisiae. Here, we report that revertant of glycogen synthase kinase mutation-1 (Rog1p) possesses monoacylglycerol (MAG) lipase activity in S. cerevisiae. The lipase activity of Rog1p was confirmed in two ways: through analysis of a strain with a double deletion of ROG1 and monoglyceride lipase YJU3 (yju3deltarog1delta) and by site-directed mutagenesis of the ROG1 lipase motif (GXSXG). Rog1p is localized in both the cytosol and the nucleus. Overexpression of ROG1 in a ROG1-deficient strain resulted in an accumulation of reactive oxygen species. These results suggest that Rog1p is a MAG lipase that regulates lipid homeostasis.
ESTHER : Vishnu_2015_FEBS.Lett_589_23
PubMedSearch : Vishnu_2015_FEBS.Lett_589_23
PubMedID: 25433290
Gene_locus related to this paper: yeast-ROG1