PDBsum entry 1jii

Ligase

PDB id: 1jii

Contents

Protein chain

319 a.a. *

Ligands

383

* Residue conservation analysis

PDB id:

1jii

Name:

Ligase

Title:

Crystal structure of s. Aureus tyrrs in complex with sb-219383

Structure:

Tyrosyl-tRNA synthetase. Chain: a. Synonym: tyrosine--tRNA ligase. Tyrrs. Tyrosyl-transfer RNA synthetase. Engineered: yes

Source:

Staphylococcus aureus. Organism_taxid: 1280. Variant: aureus n315. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

3.20Å R-factor: 0.269 R-free: 0.335

Authors:

X.Qiu,C.A.Janson,W.W.Smith,R.L.Jarvest

Key ref:

X.Qiu et al. (2001). Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors. Protein Sci, 10, 2008-2016. PubMed id: 11567092 DOI: 10.1110/ps.18001

Date:

02-Jul-01 Release date: 26-Oct-01

Protein chain

A6QHR2  (SYY_STAAE) -  Tyrosine--tRNA ligase from Staphylococcus aureus (strain Newman)

Seq: 420 a.a.

Struc: 319 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 (Bound ligand (Het Group name = 383) matches with 40.00% similarity) + ATP = L-tyrosyl-tRNA(Tyr) + AMP + diphosphate + H(+)

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

reference

DOI no: 10.1110/ps.18001

Protein Sci 10:2008-2016 (2001)

PubMed id: 11567092

Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors.

X.Qiu, C.A.Janson, W.W.Smith, S.M.Green, P.McDevitt, K.Johanson, P.Carter, M.Hibbs, C.Lewis, A.Chalker, A.Fosberry, J.Lalonde, J.Berge, P.Brown, C.S.Houge-Frydrych, R.L.Jarvest.

ABSTRACT

SB-219383 and its analogues are a class of potent and specific inhibitors of bacterial tyrosyl-tRNA synthetases. Crystal structures of these inhibitors have been solved in complex with the tyrosyl-tRNA synthetase from Staphylococcus aureus, the bacterium that is largely responsible for hospital-acquired infections. The full-length enzyme yielded crystals that diffracted to 2.8 A resolution, but a truncated version of the enzyme allowed the resolution to be extended to 2.2 A. These inhibitors not only occupy the known substrate binding sites in unique ways, but also reveal a butyl binding pocket. It was reported that the Bacillus stearothermophilus TyrRS T51P mutant has much increased catalytic activity. The S. aureus enzyme happens to have a proline at position 51. Therefore, our structures may contribute to the understanding of the catalytic mechanism and provide the structural basis for designing novel antimicrobial agents.

Selected figure(s)

Figure 7.
Fig. 7. The binding of SB-284485 to YRS. (A) Schematic diagram showing all the hydrogen bonding interactions (dashed lines) between the inhibitor and YRS. The hydrogen bonding distances are labeled. (B) Stereoview of the fucose binding mode. Hydrogen bonds are shown in dashed lines. SB-243545 is included for comparison. Protein carbons are in yellow, SB-284485 carbons are in purple, and SB-243545 carbons are in grey. Oxygen is red and nitrogen is cyan. (C) Stereoview of the superposition of SB-284485 (purple) and tyrosyl adenylate (green). The latter is shown with ribose hydrogen bonds and is modeled based on bsTyrRS structures.

Figure 8.
Fig. 8. Stereoviews of the Electron Density (2Fo-Fc) Maps for the YRS Inhibitors. (A) The density for SB-219383 contoured at 1 . (B) The density of SB239629 contoured at 1 . (C) The density for SB-243545 contoured at 1 . (D) The density for SB-284485 contoured at 1.5 .

The above figures are reprinted by permission from the Protein Society: Protein Sci (2001, 10, 2008-2016) copyright 2001.

Figures were selected by an automated process.