Literature summary for 6.1.1.6 extracted from

Khan, S.; Sharma, A.; Belrhali, H.; Yogavel, M.; Sharma, A.
Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin (2014), J. Struct. Funct. Genomics, 15, 63-71 .

Application

Application	Comment	Organism
pharmacology	Plasmodium falciparum lysyl-tRNA synthetase (PfKRS) as the cellular target for cladosporin activity. Targeting parasitic aminoacyl-tRNA synthetases (aaRSs) can provide an additional component in the present multi-drug cocktail therapy against malaria	Plasmodium falciparum

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified enzyme PfKRS in complex with lysine and cladosporin, hanging drop vapour diffusion method, mixing of 0.001 ml of highly pure enzyme in 50 mM Tris-HCl, pH 8.0, 200 mM NaCl, 10 mM 2-mercaptoethanol, 0.5 mM cladosporin, and 2 mM L-lysine, with 0.001 ml of crstallization solution containing 0.1 M Bis-Tris, pH 6.5, 2% v/v Tascimate, pH 6.0, 20% w/v PEG 3350, 20°C, 10 days, X-ray diffraction structure determination and analysis at 2.7 A resolution, molecular homology modeling using the human enzyme structure as template	Plasmodium falciparum

Crystallization (Comment)

Organism

purified enzyme PfKRS in complex with lysine and cladosporin, hanging drop vapour diffusion method, mixing of 0.001 ml of highly pure enzyme in 50 mM Tris-HCl, pH 8.0, 200 mM NaCl, 10 mM 2-mercaptoethanol, 0.5 mM cladosporin, and 2 mM L-lysine, with 0.001 ml of crstallization solution containing 0.1 M Bis-Tris, pH 6.5, 2% v/v Tascimate, pH 6.0, 20% w/v PEG 3350, 20°C, 10 days, X-ray diffraction structure determination and analysis at 2.7 A resolution, molecular homology modeling using the human enzyme structure as template

Plasmodium falciparum

Inhibitors

Inhibitors	Comment	Organism	Structure
cladosporin	has the ability to mimic the natural substrate adenosine and thereby colonize the PfKRS active site, binding structure analysis, overview. Plasmodium falciparum lysyl-tRNA synthetase (PfKRS) as the cellular target for cladosporin activity. Structural basis of inhibition by cladosporin, overview. The isocoumarin moiety of cladosporin stacks between Ph342 and Arg559 in PfKRS. In addition, His338 provides edge-toface interaction with hydroxybenzene ring of isocoumarin moiety. The THP ring points towards L-Lys binding pocket and its methyl group faces Ser344	Plasmodium falciparum

Organism

Organism	UniProt	Comment	Textmining
Plasmodium falciparum	Q8IDJ8	-	-

Synonyms

Synonyms	Comment	Organism
Lysyl-tRNA synthetase	-	Plasmodium falciparum
PF3D7_1350100	-	Plasmodium falciparum
PfKRS	-	Plasmodium falciparum