4H02

Crystal structure of P. falciparum Lysyl-tRNA synthetase

Summary for 4H02

• Entry DOI: 10.2210/pdb4h02/pdb
• Related: 3BJU
• Descriptor: Lysyl-tRNA synthetase (2 entities in total)
• Functional Keywords: cladosporin, malaria, ligase
• Biological source: Plasmodium falciparum
• Total number of polymer chains: 8
• Total formula weight: 469655.47

Authors

Khan, S.,Garg, A.,Sharma, A. (deposition date: 2012-09-07, release date: 2013-05-01, Last modification date: 2024-02-28)

Primary citation

Khan, S.,Garg, A.,Camacho, N.,Van Rooyen, J.,Kumar Pole, A.,Belrhali, H.,Ribas de Pouplana, L.,Sharma, V.,Sharma, A.
Structural analysis of malaria-parasite lysyl-tRNA synthetase provides a platform for drug development.
Acta Crystallogr.,Sect.D, 69:785-795, 2013

PubMed Abstract: Aminoacyl-tRNA synthetases are essential enzymes that transmit information from the genetic code to proteins in cells and are targets for antipathogen drug development. Elucidation of the crystal structure of cytoplasmic lysyl-tRNA synthetase from the malaria parasite Plasmodium falciparum (PfLysRS) has allowed direct comparison with human LysRS. The authors' data suggest that PfLysRS is dimeric in solution, whereas the human counterpart can also adopt tetrameric forms. It is shown for the first time that PfLysRS is capable of synthesizing the signalling molecule Ap4a (diadenosine tetraphosphate) using ATP as a substrate. The PfLysRS crystal structure is in the apo form, such that binding to ATP will require rotameric changes in four conserved residues. Differences in the active-site regions of parasite and human LysRSs suggest the possibility of exploiting PfLysRS for selective inhibition. These investigations on PfLysRS further validate malarial LysRSs as attractive antimalarial targets and provide new structural space for the development of inhibitors that target pathogen LysRSs selectively.

PubMed: 23633587
DOI: 10.1107/S0907444913001923

Experimental method

X-RAY DIFFRACTION (2.905 Å)