3KO7
DTD from Plasmodium falciparum in complex with D-Lysine
Summary for 3KO7
| Entry DOI | 10.2210/pdb3ko7/pdb |
| Related | 3KNF 3KNP 3KO3 3KO4 3KO5 3KO9 3KOB 3KOC 3KOD |
| Descriptor | D-tyrosyl-tRNA(Tyr) deacylase, D-LYSINE (3 entities in total) |
| Functional Keywords | dtd, deacylase, d-amino acid, d-lysine, hydrolase |
| Biological source | Plasmodium falciparum |
| Cellular location | Cytoplasm : Q8IIS0 |
| Total number of polymer chains | 6 |
| Total formula weight | 115544.69 |
| Authors | Manickam, Y.,Bhatt, T.K.,Sharma, A. (deposition date: 2009-11-13, release date: 2009-12-01, Last modification date: 2024-04-03) |
| Primary citation | Bhatt, T.K.,Yogavel, M.,Wydau, S.,Berwal, R.,Sharma, A. Ligand-bound Structures Provide Atomic Snapshots for the Catalytic Mechanism of D-Amino Acid Deacylase J.Biol.Chem., 285:5917-5930, 2010 Cited by PubMed Abstract: D-tyrosyl-tRNA(Tyr) deacylase (DTD) is an editing enzyme that removes D-amino acids from mischarged tRNAs. We describe an in-depth analysis of the malaria parasite Plasmodium falciparum DTD here. Our data provide structural insights into DTD complexes with adenosine and D-amino acids. Bound adenosine is proximal to the DTD catalysis site, and it represents the authentic terminal adenosine of charged tRNA. DTD-bound D-amino acids cluster at three different subsites within the overall active site pocket. These subsites, called transition, active, and exit subsites allow docking, re-orientation, chiral selection, catalysis, and exit of the free D-amino acid from DTD. Our studies reveal variable modes of D-amino acid recognition by DTDs, suggesting an inherent plasticity that can accommodate all D-amino acids. An in-depth analysis of native, ADP-bound, and D-amino acid-complexed DTD structures provide the first atomic snapshots of ligand recognition and subsequent catalysis by this enzyme family. We have mapped sites for the deacylation reaction and mark possible routes for entry and egress of all substrates and products. We have also performed structure-based inhibitor discovery and tested lead compounds against the malaria parasite P. falciparum using growth inhibition assays. Our studies provide a comprehensive structural basis for the catalytic mechanism of DTD enzymes and have implications for inhibition of this enzyme in P. falciparum as a route to inhibiting the parasite. PubMed: 20007323DOI: 10.1074/jbc.M109.038562 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.21 Å) |
Structure validation
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