3PD2

Crystal structure of the editing domain of threonyl-tRNA synthetase from Pyrococcus abyssi in complex with seryl-3'-aminoadenosine

Summary for 3PD2

• Entry DOI: 10.2210/pdb3pd2/pdb
• Related: 1y2q 2hl0 2hl1 2hl2 3PD3 3PD4 3PD5
• Descriptor: Threonyl-tRNA synthetase, SERINE-3'-AMINOADENOSINE (3 entities in total)
• Functional Keywords: alpha/beta fold, deacylase, editing, aminoacyl-trna synthetase, translation, ligase
• Biological source: Pyrococcus abyssi
• Cellular location: Cytoplasm (By similarity): Q9UZ14
• Total number of polymer chains: 2
• Total formula weight: 34183.29

Authors

Hussain, T.,Kamarthapu, V.,Kruparani, S.P.,Sankaranarayanan, R. (deposition date: 2010-10-22, release date: 2010-12-08, Last modification date: 2023-11-01)

Primary citation

Hussain, T.,Kamarthapu, V.,Kruparani, S.P.,Deshmukh, M.V.,Sankaranarayanan, R.
Mechanistic insights into cognate substrate discrimination during proofreading in translation
Proc.Natl.Acad.Sci.USA, 107:22117-22121, 2010

PubMed 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.

PubMed: 21098258
DOI: 10.1073/pnas.1014299107

Experimental method

X-RAY DIFFRACTION (1.86 Å)