title: An appended domain results in an unusual architecture for malaria parasite tryptophanyl-tRNA synthetase.
abstract: Specific activation of amino acids by aminoacyl-tRNA synthetases (aaRSs) is essential for maintaining fidelity during protein translation. Here, we present crystal structure of malaria parasite Plasmodium falciparum tryptophanyl-tRNA synthetase (Pf-WRS) catalytic domain (AAD) at 2.6 Å resolution in complex with L-tryptophan. Confocal microscopy-based localization data suggest cytoplasmic residency of this protein. Pf-WRS has an unusual N-terminal extension of AlaX-like domain (AXD) along with linker regions which together seem vital for enzymatic activity and tRNA binding. Pf-WRS is not proteolytically processed in the parasites and therefore AXD likely provides tRNA binding capability rather than editing activity. The N-terminal domain containing AXD and linker region is monomeric and would result in an unusual overall architecture for Pf-WRS where the dimeric catalytic domains have monomeric AXDs on either side. Our PDB-wide comparative analyses of 47 WRS crystal structures also provide new mechanistic insights into this enzyme family in context conserved KMSKS loop conformations.
authors.affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Sameena
authors.initials: S
authors.lastname: Khan
authors.forename: Ankur
authors.initials: A
authors.lastname: Garg
authors.forename: Arvind
authors.initials: A
authors.lastname: Sharma
authors.forename: Noelia
authors.initials: N
authors.lastname: Camacho
authors.forename: Daria
authors.initials: D
authors.lastname: Picchioni
authors.forename: Adélaïde
authors.initials: A
authors.lastname: Saint-Léger
authors.forename: Lluís
authors.initials: L
authors.lastname: Ribas de Pouplana
authors.forename: Manickam
authors.initials: M
authors.lastname: Yogavel
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
mesh_terms: D002852:Chromatography, Ion Exchange; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli; D005455:Fluorescent Antibody Technique; D018613:Microscopy, Confocal; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation; D014364:Tryptophan / Q000737:chemistry*; D014369:Tryptophan-tRNA Ligase / Q000737:chemistry*
chemical_list: D014364:Tryptophan; D014369:Tryptophan-tRNA Ligase