4eg8

Trypanosoma brucei methionyl-tRNA synthetase in complex with compound Chem 89

spinqualitylabelsall models 4eg8, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4eg8 is a 2 chain structure with sequence from Trypanosoma brucei brucei TREU927. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.596Å Ligands: 0P6, CAS, DMS, GOL, MET Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q38C91_TRYB2 Publication Abstract from PubMed To guide development of new drugs targeting methionyl-tRNA synthetase (MetRS) for treatment of human African trypanosomiasis, crystal structure determinations of Trypanosoma brucei MetRS in complex with its substrate methionine and its intermediate product methionyl-adenylate were followed by those of the enzyme in complex with high-affinity aminoquinolone inhibitors via soaking experiments. Drastic changes in conformation of one of the two enzymes in the asymmetric unit allowed these inhibitors to occupy an enlarged methionine pocket and a new so-called auxiliary pocket. Interestingly, a small low-affinity compound caused the same conformational changes, removed the methionine without occupying the methionine pocket, and occupied the previously not existing auxiliary pocket. Analysis of these structures indicates that the binding of the inhibitors is the result of conformational selection, not induced fit. Distinct States of Methionyl-tRNA Synthetase Indicate Inhibitor Binding by Conformational Selection.,Koh CY, Kim JE, Shibata S, Ranade RM, Yu M, Liu J, Gillespie JR, Buckner FS, Verlinde CL, Fan E, Hol WG Structure. 2012 Aug 14. PMID:22902861 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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