PDBsum entry 2pid

Ligase

PDB id: 2pid

Contents

Protein chain

317 a.a. *

Ligands

YSA ×2

Waters ×90

* Residue conservation analysis

PDB id:

2pid

Name:

Ligase

Title:

Crystal structure of human mitochondrial tyrosyl-tRNA synthetase in complex with an adenylate analog

Structure:

Tyrosyl-tRNA synthetase. Chain: a, b. Fragment: residues 28-375. Synonym: tyrosine-tRNA ligase, tyrrs. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: yars2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.193 R-free: 0.244

Authors:

L.Bonnefond,M.Frugier,E.Touze,B.Lorber,C.Florentz,R.Giege,C.Sauter, J.Rudinger-Thirion

Key ref:

L.Bonnefond et al. (2007). Crystal structure of human mitochondrial tyrosyl-tRNA synthetase reveals common and idiosyncratic features. Structure, 15, 1505-1516. PubMed id: 17997975 DOI: 10.1016/j.str.2007.09.018

Date:

13-Apr-07 Release date: 23-Oct-07

Protein chains

Q9Y2Z4  (SYYM_HUMAN) -  Tyrosine--tRNA ligase, mitochondrial from Homo sapiens

Seq: 477 a.a.

Struc: 317 a.a.

Enzyme reactions

• Enzyme class: E.C.6.1.1.1 - tyrosine--tRNA ligase.
• Reaction: tRNA(Tyr) + L-tyrosine + ATP = L-tyrosyl-tRNA(Tyr) + AMP + diphosphate + H⁺

tRNA(Tyr) + L-tyrosine + ATP = L-tyrosyl-tRNA(Tyr) (Bound ligand (Het Group name = YSA) matches with 48.72% similarity) + AMP + diphosphate + H(+)

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

reference

DOI no: 10.1016/j.str.2007.09.018

Structure 15:1505-1516 (2007)

PubMed id: 17997975

Crystal structure of human mitochondrial tyrosyl-tRNA synthetase reveals common and idiosyncratic features.

L.Bonnefond, M.Frugier, E.Touzé, B.Lorber, C.Florentz, R.Giegé, C.Sauter, J.Rudinger-Thirion.

ABSTRACT

We report the structure of a strictly mitochondrial human synthetase, namely tyrosyl-tRNA synthetase (mt-TyrRS), in complex with an adenylate analog at 2.2 A resolution. The structure is that of an active enzyme deprived of the C-terminal S4-like domain and resembles eubacterial TyrRSs with a canonical tyrosine-binding pocket and adenylate-binding residues typical of class I synthetases. Two bulges at the enzyme surface, not seen in eubacterial TyrRSs, correspond to conserved sequences in mt-TyrRSs. The synthetase electrostatic surface potential differs from that of other TyrRSs, including the human cytoplasmic homolog and the mitochondrial one from Neurospora crassa. The homodimeric human mt-TyrRS shows an asymmetry propagating from the dimer interface toward the two catalytic sites and extremities of each subunit. Mutagenesis of the catalytic domain reveals functional importance of Ser200 in line with an involvement of A73 rather than N1-N72 in tyrosine identity.

Selected figure(s)

Figure 3.
Figure 3. Conformational Asymmetry in Homodimeric Human mt-TyrRS-ΔS4
Superimposition of the two subunits of mt-TyrRS-ΔS4 in complex with Tyr-AMS (backbones colored as in Figure 1A, in heavy and light colors for monomer A and B, respectively). The regions with largest asymmetries are circled. Note that the two adenylate analogs (in blue) almost perfectly superimpose.

Figure 7.
Figure 7. Role of Clusters 1 and 2 in tRNA^Tyr Acceptor Arm Recognition
(A) Superimposition of the cleft formed by the two helical structures of clusters 1 and 2 (in which binds the tyrosine acceptor arm of tRNA^Tyr) in the crystallographic structures of human mt-TyrRS (in brown), B. stearothermophilus TyrRS (in blue), and T. thermophilus TyrRS in complex with tRNA^Tyr (in green). Notice the quasiperfect superimposition of the two clusters in human mt-TyrRS and B. stearothermophilus TyrRS and the important structural deviations in T. thermophilus TyrRS. The bar at the bottom of the figure shows the position where the cleft is largest (d = 9.9, 10.0, and 12.4 Å in the TyrRSs from human mitochondria, B. stearothermophilus, and T. thermophilus, respectively, indicating an enlargement of the cleft in T. thermophilus of vert, similar 2.5 Å). The three amino acids that were mutagenized are indicated.
(B) View of the clusters and their proximity with the tRNA acceptor branch as seen in the crystal structure of the T. thermophilus complex (Yaremchuk et al., 2002).

The above figures are reprinted by permission from Cell Press: Structure (2007, 15, 1505-1516) copyright 2007.

Figures were selected by an automated process.