6LDK
Isoleucyl-tRNA synthetase from Candida albicans complexed with a isoleucyl-adenylate
Summary for 6LDK
| Entry DOI | 10.2210/pdb6ldk/pdb |
| Descriptor | Isoleucine--tRNA ligase, ADENOSINE MONOPHOSPHATE, ISOLEUCINE, ... (4 entities in total) |
| Functional Keywords | trna synthetase, translation |
| Biological source | Candida albicans SC5314 |
| Total number of polymer chains | 1 |
| Total formula weight | 99829.76 |
| Authors | |
| Primary citation | Chung, S.,Kim, S.,Ryu, S.H.,Hwang, K.Y.,Cho, Y. Structural Basis for the Antibiotic Resistance of Eukaryotic Isoleucyl-tRNA Synthetase. Mol.Cells, 43:350-359, 2020 Cited by PubMed Abstract: Pathogenic aminoacyl-tRNA synthetases (ARSs) are attractive targets for anti-infective agents because their catalytic active sites are different from those of human ARSs. Mupirocin is a topical antibiotic that specifically inhibits bacterial isoleucy-ltRNA synthetase (IleRS), resulting in a block to protein synthesis. Previous studies on IleRS indicated that mupirocin-resistance of eukaryotic IleRS is primarily due to differences in two amino acids, His581 and Leu583, in the active site. However, without a eukaryotic IleRS structure, the structural basis for mupirocin-resistance of eukaryotic IleRS remains elusive. Herein, we determined the crystal structure of IleRS complexed with Ile-AMP at 2.9 Å resolution. The largest difference between eukaryotic and prokaryotic IleRS enzymes is closure of the active site pocket by Phe55 in the HIGH loop; Arg410 in the CP core loop; and the second Lys in the KMSKR loop. The Ile-AMP product is lodged in a closed active site, which may restrict its release and thereby enhance catalytic efficiency. The compact active site also prevents the optimal positioning of the 9-hydroxynonanoic acid of mupirocin and plays a critical role in resistance of eukaryotic IleRS to anti-infective agents. PubMed: 32088946DOI: 10.14348/molcells.2020.2287 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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