4PG3
Crystal structure of KRS complexed with inhibitor
Summary for 4PG3
| Entry DOI | 10.2210/pdb4pg3/pdb |
| Descriptor | Lysine--tRNA ligase, LYSINE, cladosporin, ... (4 entities in total) |
| Functional Keywords | inhibitor, krs, complex, ligase-ligase inhibitor complex, ligase/ligase inhibitor |
| Biological source | Plasmodium falciparum |
| Total number of polymer chains | 4 |
| Total formula weight | 236585.82 |
| Authors | Sharma, A.,Yogavel, M.,Khan, S.,Sharma, A.,Belrhali, H. (deposition date: 2014-05-01, release date: 2014-07-16, Last modification date: 2023-09-27) |
| Primary citation | Khan, S.,Sharma, A.,Belrhali, H.,Yogavel, M.,Sharma, A. Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin. J. Struct. Funct. Genomics, 15:63-71, 2014 Cited by PubMed Abstract: Malaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin's remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase. PubMed: 24935905DOI: 10.1007/s10969-014-9182-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.696 Å) |
Structure validation
Download full validation report
