4nbi

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D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with D-tyrosyl-3'-aminoadenosine at 1.86 Angstrom resolution

Structural highlights

4nbi is a 2 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.86Å
Ligands:D3Y, PGE
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).[1] [2] [3] [4]

Publication Abstract from PubMed

The biological macromolecular world is homochiral and effective enforcement and perpetuation of this homochirality is essential for cell survival. In this study, we present the mechanistic basis of a configuration-specific enzyme that selectively removes D-amino acids erroneously coupled to tRNAs. The crystal structure of dimeric D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with a substrate-mimicking analog shows how it uses an invariant 'cross-subunit' Gly-cisPro dipeptide to capture the chiral centre of incoming D-aminoacyl-tRNA. While no protein residues are directly involved in catalysis, the unique side chain-independent mode of substrate recognition provides a clear explanation for DTD's ability to act on multiple D-amino acids. The strict chiral specificity elegantly explains how the enriched cellular pool of L-aminoacyl-tRNAs escapes this proofreading step. The study thus provides insights into a fundamental enantioselection process and elucidates a chiral enforcement mechanism with a crucial role in preventing D-amino acid infiltration during the evolution of translational apparatus. DOI: http://dx.doi.org/10.7554/eLife.01519.001.

Mechanism of chiral proofreading during translation of the genetic code.,Ahmad S, Routh SB, Kamarthapu V, Chalissery J, Muthukumar S, Hussain T, Kruparani SP, Deshmukh MV, Sankaranarayanan R Elife. 2013 Dec 3;2(0):e01519. doi: 10.7554/eLife.01519. PMID:24302572[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
1 reviews cite this structure
Macromolecular structures: Quality assessment and biological interpretation.
Salunke et al. (2017)
0 more
7 other articles
No citations found

References

  1. ↑ Bhatt TK, Yogavel M, Wydau S, Berwal R, Sharma A. Ligand-bound structures provide atomic snapshots for the catalytic mechanism of D-amino acid deacylase. J Biol Chem. 2010 Feb 19;285(8):5917-30. Epub 2009 Dec 9. PMID:20007323 doi:10.1074/jbc.M109.038562
  2. ↑ Ahmad S, Routh SB, Kamarthapu V, Chalissery J, Muthukumar S, Hussain T, Kruparani SP, Deshmukh MV, Sankaranarayanan R. Mechanism of chiral proofreading during translation of the genetic code. Elife. 2013 Dec 3;2(0):e01519. doi: 10.7554/eLife.01519. PMID:24302572 doi:http://dx.doi.org/10.7554/eLife.01519
  3. ↑ Routh SB, Pawar KI, Ahmad S, Singh S, Suma K, Kumar M, Kuncha SK, Yadav K, Kruparani SP, Sankaranarayanan R. Elongation Factor Tu Prevents Misediting of Gly-tRNA(Gly) Caused by the Design Behind the Chiral Proofreading Site of D-Aminoacyl-tRNA Deacylase. PLoS Biol. 2016 May 25;14(5):e1002465. doi: 10.1371/journal.pbio.1002465., eCollection 2016 May. PMID:27224426 doi:http://dx.doi.org/10.1371/journal.pbio.1002465
  4. ↑ Pawar KI, Suma K, Seenivasan A, Kuncha SK, Routh SB, Kruparani SP, Sankaranarayanan R. Role of D-aminoacyl-tRNA deacylase beyond chiral proofreading as a cellular defense against glycine mischarging by AlaRS. Elife. 2017 Mar 31;6:e24001. doi: 10.7554/eLife.24001. PMID:28362257 doi:http://dx.doi.org/10.7554/eLife.24001
  5. ↑ Ahmad S, Routh SB, Kamarthapu V, Chalissery J, Muthukumar S, Hussain T, Kruparani SP, Deshmukh MV, Sankaranarayanan R. Mechanism of chiral proofreading during translation of the genetic code. Elife. 2013 Dec 3;2(0):e01519. doi: 10.7554/eLife.01519. PMID:24302572 doi:http://dx.doi.org/10.7554/eLife.01519

Contents


PDB ID 4nbi

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