Monday, October 17, 2016

Hello!! Find and follow me at

www.linkedin.com/in/vituljain123

and

https://www.researchgate.net/profile/Vitul_Jain

and

https://www.instagram.com/jainvitul/

and finally at

https://twitter.com/vituljain

Saturday, August 6, 2016

Dimerization of Arginyl-tRNA Synthetase

by Free Heme Drives Its Inactivation in

Plasmodium falciparum

http://www.cell.com/structure/abstract/S0969-2126(16)30164-2

Abstract

Excess cellular heme is toxic, and malaria parasites regulate its levels during hemoglobin digestion. Aminoacyl-tRNA synthetases are ubiquitous enzymes, and of these, arginyl-tRNA synthetase (RRS) is unique as its enzymatic product of charged tRNA is required for protein synthesis and degradation. We show that Plasmodium falciparum arginyl-tRNA synthetase (PfRRS) is an active, cytosolic, and monomeric enzyme. Its high-resolution crystal structure highlights critical structural differences with the human enzyme. We further show that hemin binds to and inhibits the aminoacylation activity of PfRRS. Hemin induces a dimeric form of PfRRS that is thus rendered enzymatically dead as it is unable to recognize its cognate tRNAarg. Excessive hemin in chloroquine-treated malaria parasites results in significantly reduced charged tRNAarg levels, thus suggesting deceleration of protein synthesis. These data together suggest that the inhibition of Plasmodium falciparum arginyl-tRNA synthetase can now be synergized with existing antimalarials for more potent drug cocktails against malaria parasites.

Structure of Prolyl-tRNA Synthetase-Halofuginone

Complex Provides Basis for Development of Drugs

against Malaria and Toxoplasmosis

http://www.cell.com/structure/abstract/S0969-2126(15)00074-X

Abstract

The Chinese herb Dichroa febrifuga has traditionally treated malaria-associated fever. Its active component febrifugine (FF) and derivatives such as halofuginone (HF) are potent anti-malarials. Here, we show that FF-based derivatives arrest parasite growth by direct interaction with and inhibition of the protein translation enzyme prolyl-tRNA synthetase (PRS). Dual administration of inhibitors that target different tRNA synthetases suggests high utility of these drug targets. We reveal the ternary complex structure of PRS-HF and adenosine 5′-(β,γ-imido)triphosphate where the latter facilitates HF integration into the PRS active site. Structural analyses also highlight spaces within the PRS architecture for HF derivatization of its quinazolinone, but not piperidine, moiety. We also show a remarkable ability of HF to kill the related human parasite Toxoplasma gondii, suggesting wider HF efficacy against parasitic PRSs. Hence, our cell-, enzyme-, and structure-based data on FF-based inhibitors strengthen the case for their inclusion in anti-malarial and anti-toxoplasmosis drug development efforts.

Sunday, January 11, 2009

nice sites

http://www.pinkmonkey.com/studyguides/subjects/biology-edited/contents.asp

Monday, January 5, 2009

ebooks

BBotany Illustrated: Introduction to Plants, Major Groups, Flowering Plant Families

http://rapidshare.com/files/153220362/68F03E69-B003-4AE8-B65E-F3AC3921CEB3.rar

Molecular biology of gene by J.D.Watson

http://rapidshare.com/files/107105097/Watson_J.D._Molecular_Biology_of_the_Gene__5th_edition_.pdfotany Illustrated: Introduction to Plants, Major Groups, Flowering Plant Families

http://rapidshare.com/files/153220362/68F03E69-B003-4AE8-B65E-F3AC3921CEB3.rar

Molecular biology of gene by J.D.Watson

http://rapidshare.com/files/107105097/Watson_J.D._Molecular_Biology_of_the_Gene__5th_edition_.pdf|