PDBsum entry 2dr2

Ligase/RNA

PDB id

2dr2

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Contents

			Protein chain

					373 a.a. *

			DNA/RNA

			Ligands

					SO4


					TRP

* Residue conservation analysis

PDB id:

2dr2

Links

Name:

Ligase/RNA

Title:

Structure of human tryptophanyl-tRNA synthetase in complex with tRNA(trp)

Structure:

Transfer RNA-trp. Chain: b. Synonym: tRNA(trp). Engineered: yes. Tryptophanyl-tRNA synthetase. Chain: a. Fragment: aminoacylation catalytic fragment. Synonym: tryptophan--tRNA ligase, trprs, ifp53, hwrs. Engineered: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: wars, wrs.

Biol. unit:

Tetramer (from PDB file)

Resolution:

3.00Å

R-factor:

0.228

R-free:

0.285

Authors:

N.Shen,L.Guo,B.Yang,Y.Jin,J.Ding

Key ref:

N.Shen et al. (2006). Structure of human tryptophanyl-tRNA synthetase in complex with tRNATrp reveals the molecular basis of tRNA recognition and specificity. Nucleic Acids Res, 34, 3246-3258. PubMed id: 16798914

Date:

05-Jun-06

Release date:

11-Jul-06

PROCHECK

	Headers

	References

Protein chain

P23381 (SYWC_HUMAN) - Tryptophan--tRNA ligase, cytoplasmic from Homo sapiens

Seq: Struc:					471 a.a. 373 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

DNA/RNA chain

G-A-C-C-U-C-G-U-G-G-C-G-C-A-A-U-G-G-U-A-G-C-G-C-G-U-C-U-G-A-C-U-C-C-A-G-A-U-C- 75 bases



		Enzyme reactions

Enzyme class:

E.C.6.1.1.2 - tryptophan--tRNA ligase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

tRNA(Trp) + L-tryptophan + ATP = L-tryptophyl-tRNA(Trp) + AMP + diphosphate + H⁺

tRNA(Trp)

L-tryptophan
Bound ligand (Het Group name = TRP)
corresponds exactly

ATP

L-tryptophyl-tRNA(Trp)

AMP

diphosphate

H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

	Nucleic Acids Res 34:3246-3258 (2006)
PubMed id: 16798914

Structure of human tryptophanyl-tRNA synthetase in complex with tRNATrp reveals the molecular basis of tRNA recognition and specificity.
N.Shen, L.Guo, B.Yang, Y.Jin, J.Ding.

ABSTRACT

Aminoacyl-tRNA synthetases (aaRSs) are a family of enzymes responsible for the covalent link of amino acids to their cognate tRNAs. The selectivity and species-specificity in the recognitions of both amino acid and tRNA by aaRSs play a vital role in maintaining the fidelity of protein synthesis. We report here the first crystal structure of human tryptophanyl-tRNA synthetase (hTrpRS) in complex with tRNA(Trp) and Trp which, together with biochemical data, reveals the molecular basis of a novel tRNA binding and recognition mechanism. hTrpRS recognizes the tRNA acceptor arm from the major groove; however, the 3' end CCA of the tRNA makes a sharp turn to bind at the active site with a deformed conformation. The discriminator base A73 is specifically recognized by an alpha-helix of the unique N-terminal domain and the anticodon loop by an alpha-helix insertion of the C-terminal domain. The N-terminal domain appears to be involved in Trp activation, but not essential for tRNA binding and acylation. Structural and sequence comparisons suggest that this novel tRNA binding and recognition mechanism is very likely shared by other archaeal and eukaryotic TrpRSs, but not by bacterial TrpRSs. Our findings provide insights into the molecular basis of tRNA specificity and species-specificity.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21378755

X.Agirrezabala, E.Schreiner, L.G.Trabuco, J.Lei, R.F.Ortiz-Meoz, K.Schulten, R.Green, and J.Frank (2011).
Structural insights into cognate versus near-cognate discrimination during decoding.

EMBO J, 30, 1497-1507.

PDB codes:

3izt 3izu 3izv 3izw

19768679

M.Bhattacharyya, A.Ghosh, P.Hansia, and S.Vishveshwara (2010).
Allostery and conformational free energy changes in human tryptophanyl-tRNA synthetase from essential dynamics and structure networks.

Proteins, 78, 506-517.

20969649

M.Cristodero, T.Seebeck, and A.Schneider (2010).
Mitochondrial translation is essential in bloodstream forms of Trypanosoma brucei.

Mol Microbiol, 78, 757-769.

20123733

M.Zhou, X.Dong, N.Shen, C.Zhong, and J.Ding (2010).
Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design.

Nucleic Acids Res, 38, 3399-3413.

PDB codes:

3kt0 3kt3 3kt6 3kt8

19386587

F.Charrière, P.O'Donoghue, S.Helgadóttir, L.Maréchal-Drouard, M.Cristodero, E.K.Horn, D.Söll, and A.Schneider (2009).
Dual targeting of a tRNAAsp requires two different aspartyl-tRNA synthetases in Trypanosoma brucei.

J Biol Chem, 284, 16210-16217.

19179361

W.Tsuchiya, and T.Hasegawa (2009).
Molecular recognition of tryptophan tRNA by tryptophanyl-tRNA synthetase from Aeropyrum pernix K1.

J Biochem, 145, 635-641.

18620074

I.A.Critchley, and U.A.Ochsner (2008).
Recent advances in the preclinical evaluation of the topical antibacterial agent REP8839.

Curr Opin Chem Biol, 12, 409-417.

18160411

N.J.Reiter, L.J.Maher, and S.E.Butcher (2008).
DNA mimicry by a high-affinity anti-NF-kappaB RNA aptamer.

Nucleic Acids Res, 36, 1227-1236.

PDB code:

2jwv

18180246

N.Shen, M.Zhou, B.Yang, Y.Yu, X.Dong, and J.Ding (2008).
Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states.

Nucleic Acids Res, 36, 1288-1299.

PDB codes:

2quh 2qui 2quj 2quk

17447878

I.A.Vasil'eva, and N.A.Moor (2007).
Interaction of aminoacyl-tRNA synthetases with tRNA: general principles and distinguishing characteristics of the high-molecular-weight substrate recognition.

Biochemistry (Mosc), 72, 247-263.

17726052

L.T.Guo, X.L.Chen, B.T.Zhao, Y.Shi, W.Li, H.Xue, and Y.X.Jin (2007).
Human tryptophanyl-tRNA synthetase is switched to a tRNA-dependent mode for tryptophan activation by mutations at V85 and I311.

Nucleic Acids Res, 35, 5934-5943.

17637340

X.L.Yang, M.Guo, M.Kapoor, K.L.Ewalt, F.J.Otero, R.J.Skene, D.E.McRee, and P.Schimmel (2007).
Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase.

Structure, 15, 793-805.

PDB code:

1r6u

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.