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      https://www.ias.ac.in/article/fulltext/jbsc/045/0063

    • Keywords

       

      AN2690; benzoxaborole inhibitor; CP1 domain; L. donovani ; leucyl-tRNA synthetase

    • Abstract

       

      Leucyl-tRNA synthetases (LRS) catalyze the linkage of leucine with tRNALeu. A large insertion CP1 domain(Connective Polypeptide 1) in LRS is responsible for post-transfer editing of mis-charged aminoacyl-tRNAs.Here, we characterized the CP1 domain of Leishmania donovani, a protozoan parasite, and its role in editingactivity and interaction with broad spectrum anti-fungal, AN2690. The deletion mutant of LRS, devoid of CP1domain (LRS-CP1D) was constructed, followed by determination of its role in editing and aminoacylation.Binding of AN2690 and different amino acids with CP1 deletion mutant and full length LRS was evaluatedusing isothermal titration calorimetry (ITC) and molecular dynamics simulations. The recombinant LRS-CP1 Deltaprotein did not catalyze the aminoacylation and the editing reaction when compared to full-length LRS. Thus,indicating that CP1 domain was imperative for both aminoacylation and editing activities of LRS. Bindingstudies with different amino acids indicated selectivity of isoleucine by CP1 domain over other amino acids.These studies also indicated high affinity of AN2690 with the editing domain. Molecular docking studiesindicated that AN2690-CP1 domain complex was stabilized by hydrogen bonding and hydrophobic interactionsresulting in high binding affinity between the two. Our data suggests CP1 is crucial for the function of L.donovani LRS.

    • Author Affiliations

       

      SMRITI TANDON1 REETIKA MANHAS1 NEHA TIWARI2 MANOJ MUNDE2 RAMACHANDRAN VIJAYAN1 SAMUDRALA GOURINATH1 ROHINI MUTHUSWAMI3 RENTALA MADHUBALA1

      1. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
      2. School of Physical Sciences, Jawaharlal Nehru University, New Delhi, India
      3. Chromatin Remodelling Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
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