6a88

Crystal Structure of T. gondii prolyl tRNA synthetase with Febrifugine and ATP Analog

spinqualitylabelsall models 6a88, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6a88 is a 4 chain structure with sequence from Toxoplasma gondii ME49. 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: 9SF, ANP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S8G8I1_TOXGM Publication Abstract from PubMed Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family that drives protein translation in cells. The apicomplexan PRSs are validated targets of febrifugine (FF) and its halogenated derivative halofuginone (HF). PRSs are of great interest for drug development against Plasmodium falciparum and Toxoplasma gondii. In this study, structures of apo and FF-bound T. gondii (TgPRS) are revealed and the dynamic nature of the conformational changes that occur upon FF binding is unraveled. In addition, this study highlights significant conformational plasticity within two different crystal structures of apo PRSs but not within drug-bound PRSs. The apo PRSs exist in multi-conformational states and manifest pseudo-dimeric structures. In contrast, when FF is bound the PRS dimer adopts a highly symmetrical architecture. It is shown that TgPRS does not display extant fold switching, in contrast to P. falciparum PRS, despite having over 65% sequence identity. Finally, structure-comparison analyses suggest the utility of r.m.s.d. per residue (r.m.s.d.(/res)) as a robust tool to detect structural alterations even when the r.m.s.d. is low. Apo TgPRS reveals FF/HF-induced rigidity and this work has implications for drug-design studies that rely on the apo structures of target proteins. Conformational heterogeneity in apo and drug-bound structures of Toxoplasma gondii prolyl-tRNA synthetase.,Mishra S, Malhotra N, Kumari S, Sato M, Kikuchi H, Yogavel M, Sharma A Acta Crystallogr F Struct Biol Commun. 2019 Nov 1;75(Pt 11):714-724. doi:, 10.1107/S2053230X19014808. Epub 2019 Nov 7. PMID:31702585 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminoacyl tRNA synthetase 3D structures

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