3pd5: Difference between revisions
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==Crystal structure of the editing domain of threonyl-tRNA synthetase from Pyrococcus abyssi in complex with an analog of threonyl-adenylate== | |||
<StructureSection load='3pd5' size='340' side='right'caption='[[3pd5]], [[Resolution|resolution]] 2.29Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3pd5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_abyssi Pyrococcus abyssi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PD5 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]] 2.29Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TSB:5-O-(N-(L-THREONYL)-SULFAMOYL)ADENOSINE'>TSB</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=3pd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pd5 OCA], [https://pdbe.org/3pd5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pd5 RCSB], [https://www.ebi.ac.uk/pdbsum/3pd5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pd5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SYT_PYRAB SYT_PYRAB] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Editing/proofreading by aminoacyl-tRNA synthetases is an important quality control step in the accurate translation of the genetic code that removes noncognate amino acids attached to tRNA. Defects in the process of editing result in disease conditions including neurodegeneration. While proofreading, the cognate amino acids larger by a methyl group are generally thought to be sterically rejected by the editing modules as envisaged by the "Double-Sieve Model." Strikingly using solution based direct binding studies, NMR-heteronuclear single quantum coherence (HSQC) and isothermal titration calorimetry experiments, with an editing domain of threonyl-tRNA synthetase, we show that the cognate substrate can gain access and bind to the editing pocket. High-resolution crystal structural analyses reveal that functional positioning of substrates rather than steric exclusion is the key for the mechanism of discrimination. A strategically positioned "catalytic water" molecule is excluded to avoid hydrolysis of the cognate substrate using a "RNA mediated substrate-assisted catalysis mechanism" at the editing site. The mechanistic proof of the critical role of RNA in proofreading activity is a completely unique solution to the problem of cognate-noncognate selection mechanism. | |||
Mechanistic insights into cognate substrate discrimination during proofreading in translation.,Hussain T, Kamarthapu V, Kruparani SP, Deshmukh MV, Sankaranarayanan R Proc Natl Acad Sci U S A. 2010 Nov 22. PMID:21098258<ref>PMID:21098258</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3pd5" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Aminoacyl tRNA | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pyrococcus abyssi]] | [[Category: Pyrococcus abyssi]] | ||
[[Category: Hussain T]] | |||
[[Category: Hussain | [[Category: Kamarthapu V]] | ||
[[Category: Kamarthapu | [[Category: Kruparani SP]] | ||
[[Category: Kruparani | [[Category: Sankaranarayanan R]] | ||
[[Category: Sankaranarayanan | |||
Latest revision as of 20:05, 1 November 2023
Crystal structure of the editing domain of threonyl-tRNA synthetase from Pyrococcus abyssi in complex with an analog of threonyl-adenylateCrystal structure of the editing domain of threonyl-tRNA synthetase from Pyrococcus abyssi in complex with an analog of threonyl-adenylate
Structural highlights
FunctionPublication Abstract from PubMedEditing/proofreading by aminoacyl-tRNA synthetases is an important quality control step in the accurate translation of the genetic code that removes noncognate amino acids attached to tRNA. Defects in the process of editing result in disease conditions including neurodegeneration. While proofreading, the cognate amino acids larger by a methyl group are generally thought to be sterically rejected by the editing modules as envisaged by the "Double-Sieve Model." Strikingly using solution based direct binding studies, NMR-heteronuclear single quantum coherence (HSQC) and isothermal titration calorimetry experiments, with an editing domain of threonyl-tRNA synthetase, we show that the cognate substrate can gain access and bind to the editing pocket. High-resolution crystal structural analyses reveal that functional positioning of substrates rather than steric exclusion is the key for the mechanism of discrimination. A strategically positioned "catalytic water" molecule is excluded to avoid hydrolysis of the cognate substrate using a "RNA mediated substrate-assisted catalysis mechanism" at the editing site. The mechanistic proof of the critical role of RNA in proofreading activity is a completely unique solution to the problem of cognate-noncognate selection mechanism. Mechanistic insights into cognate substrate discrimination during proofreading in translation.,Hussain T, Kamarthapu V, Kruparani SP, Deshmukh MV, Sankaranarayanan R Proc Natl Acad Sci U S A. 2010 Nov 22. PMID:21098258[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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