5j61
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with glycyl-3'-aminoadenosine at 2.10 Angstrom resolution== | |
| + | <StructureSection load='5j61' size='340' side='right'caption='[[5j61]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5j61]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J61 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J61 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A3G:3-DEOXY-3-(GLYCYLAMINO)ADENOSINE'>A3G</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5j61 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j61 OCA], [https://pdbe.org/5j61 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j61 RCSB], [https://www.ebi.ac.uk/pdbsum/5j61 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j61 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DTD_PLAF7 DTD_PLAF7] D-aminoacyl-tRNA deacylase, with no observable activity on tRNAs charged with their cognate L-amino acid (PubMed:20007323, PubMed:24302572, PubMed:27224426). Probably acts by rejecting L-amino acids from its binding site rather than specific recognition of D-amino acids (PubMed:27224426). Catalyzes the hydrolysis of D-tyrosyl-tRNA(Tyr), has no activity on correctly charged L-tyrosyl-tRNA(Tyr) (PubMed:20007323, PubMed:24302572, PubMed:27224426). Hydrolyzes correctly charged, achiral, glycyl-tRNA(Gly) (PubMed:27224426). Deacylates mischarged D.melanogaster and E.coli glycyl-tRNA(Ala) (PubMed:28362257). Probably acts via tRNA-based rather than protein-based catalysis (PubMed:24302572, PubMed:27224426). Acts on tRNAs only when the D-amino acid is either attached to the ribose 3'-OH or transferred to the 3'-OH from the 2'-OH through rapid transesterification (PubMed:24302572). Binds a number of other D-amino acids (D-Arg, D-Glu, D-His, D-Lys, D-Ser), suggesting it may also deacylate other mischarged tRNAs (PubMed:20007323).<ref>PMID:20007323</ref> <ref>PMID:24302572</ref> <ref>PMID:27224426</ref> <ref>PMID:28362257</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | D-aminoacyl-tRNA deacylase (DTD) removes D-amino acids mischarged on tRNAs and is thus implicated in enforcing homochirality in proteins. Previously, we proposed that selective capture of D-aminoacyl-tRNA by DTD's invariant, cross-subunit Gly-cisPro motif forms the mechanistic basis for its enantioselectivity. We now show, using nuclear magnetic resonance (NMR) spectroscopy-based binding studies followed by biochemical assays with both bacterial and eukaryotic systems, that DTD effectively misedits Gly-tRNAGly. High-resolution crystal structure reveals that the architecture of DTD's chiral proofreading site is completely porous to achiral glycine. Hence, L-chiral rejection is the only design principle on which DTD functions, unlike other chiral-specific enzymes such as D-amino acid oxidases, which are specific for D-enantiomers. Competition assays with elongation factor thermo unstable (EF-Tu) and DTD demonstrate that EF-Tu precludes Gly-tRNAGly misediting at normal cellular concentrations. However, even slightly higher DTD levels overcome this protection conferred by EF-Tu, thus resulting in significant depletion of Gly-tRNAGly. Our in vitro observations are substantiated by cell-based studies in Escherichia coli that show that overexpression of DTD causes cellular toxicity, which is largely rescued upon glycine supplementation. Furthermore, we provide direct evidence that DTD is an RNA-based catalyst, since it uses only the terminal 2'-OH of tRNA for catalysis without the involvement of protein side chains. The study therefore provides a unique paradigm of enzyme action for substrate selection/specificity by DTD, and thus explains the underlying cause of DTD's activity on Gly-tRNAGly. It also gives a molecular and functional basis for the necessity and the observed tight regulation of DTD levels, thereby preventing cellular toxicity due to misediting. | ||
| - | + | Elongation Factor Tu Prevents Misediting of Gly-tRNA(Gly) Caused by the Design Behind the Chiral Proofreading Site of D-Aminoacyl-tRNA Deacylase.,Routh SB, Pawar KI, Ahmad S, Singh S, Suma K, Kumar M, Kuncha SK, Yadav K, Kruparani SP, Sankaranarayanan R PLoS Biol. 2016 May 25;14(5):e1002465. doi: 10.1371/journal.pbio.1002465., eCollection 2016 May. PMID:27224426<ref>PMID:27224426</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5j61" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Plasmodium falciparum 3D7]] | ||
| + | [[Category: Ahmad S]] | ||
| + | [[Category: Routh SB]] | ||
| + | [[Category: Sankaranarayanan R]] | ||
Current revision
D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with glycyl-3'-aminoadenosine at 2.10 Angstrom resolution
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