3PD3: Crystal Structure Of The Editing Domain Of Threonyl-Trna Synthetase From Pyrococcus Abyssi In Complex With Threonyl-3'-Aminoadenosine

Citation:
Abstract
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.
PDB ID: 3PD3Download
MMDB ID: 87229
PDB Deposition Date: 2010/10/22
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 1.86  Å
Source Organism:
Similar Structures:
Biological Unit for 3PD3: dimeric; determined by author and by software (PISA)
Molecular Components in 3PD3
Label Count Molecule
Proteins (2 molecules)
2
Threonyl-trna Synthetase(Gene symbol: PAB_RS07200)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

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