PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Cas4 Nuclease and Bacterial Immunity
February 2014
Protein-Nucleic Acid Interaction: Inhibition Through Allostery
July 2013
Stabilizing DNA Single Strands
July 2013
AlkB Homologs
August 2012
Methyl maintenance
May 2012
Follow the RNA leader
December 2011
RNA Chaperone NMB1681
July 2011
Seeing HetR
July 2011
Structure from sequence
July 2011
Added benefits
April 2011
Nitrile Reductase QueF
March 2011
Inhibiting factor
February 2011
Tryptophanyl-tRNA Synthetase
February 2011
Regulating nitrogen assimilation
January 2011
Subtle shifts
January 2011
tRNA Isopentenyltransferase MiaA
August 2010
Mre11 Nuclease
May 2010
Seek and destroy 8-oxoguanine
May 2010
Antibiotics and Ribosome Function
March 2010
Pseudouridine Synthase TruA
November 2009
Get3 into the groove
October 2009
Guanine Nucleotide Exchange Factor Vav1 and Rho GTPase Rac1
October 2009
Proofreading RNA
July 2009
Hda and DNA Replication
June 2009
The elusive helicase
April 2009
Poly(A) RNA recognition
January 2009
Scavenger Decapping Enzyme DcpS
November 2008
Bacteriophage Lambda cII Protein
October 2008
RNase T
July 2008
SARS Coronavirus Nonstructural Protein 1
June 2008

Research Themes DNA and RNA

Tryptophanyl-tRNA Synthetase

SBKB [doi:10.3942/psi_sgkb/fm_2011_2]
Featured System - February 2011
Short description: Biology is full of surprises, and they often tell us important things about ourselves.

Biology is full of surprises, and they often tell us important things about ourselves. Crystallography is no exception: often, unexpected things appear once a structure is solved. The recent structure of a bacterial tryptophanyl-tRNA synthetase, solved by researchers at JCSG, revealed two unexpected features.

Iron Strength

The biggest surprise in the structure, available in PDB entry 2g36, was the discovery of an iron-sulfur cluster. Tryptophanyl-tRNA synthetase is an elongated dimeric enzyme, with the tryptophan-adding machinery at near the center, and the tRNA-recognizing elements at the two ends. The active site is very similar to the enzymes from other organisms, but the tRNA-recognizing portion is built around four cysteines, which together trap an iron-sulfur cluster.

A Happy Accident

A second surprise occurred in the active site: the crystals include a molecule of tryptophan bound in each subunit of the enzyme. This came as a surprise, since tryptophan was not added to the mixture of molecules used to crystallize the enzyme. So, these tryptophan molecules must have hitchhiked along with the enzyme through the entire process of expression and purification, ultimately showing up in the electron density map. This is a reflection of the tight binding and specificity of the active site for tryptophan, which is essential for its function in adding the proper amino acid to its target tRNA.

Why Iron?

The presence of tryptophan in the structure is easily explained, but why is there an iron-sulfur cluster? This is the first time that an iron-sulfur cluster has been seen in aminoacyl-tRNA synthetases, but after searching through genomic sequences, a similar four-cysteine motif was found in a variety of other species. Also, given that iron-sulfur clusters are rather expensive to construct, we might guess that it's playing an important functional role. Researchers at PSI have hypothesized that the cluster may be needed to recognize the particular modifications of the tRNA, but a definitive answer will have to wait until these tRNA modifications are fully characterized.
To take a look at the Thermotoga enzyme and a model of how tRNA binds, click on the image of the iron-sulfur cluster for an interactive Jmol. To learn more about the protein or make a comment about the possible role of the iron-sulfur cluster, take a look at the page at TOPSAN.

The JSmol tab below displays an interactive JSmol

Potassium Ion Transporter TrkH (PDB entry 3pjz)

The selectivity filter of TrkH includes a precise array of oxygen atoms that mimic the water structure around a free potassium ion. In this Jmol image, the potassium ion is shown in magenta, surrounded by the eight oxygens provided by the protein peptide groups. Use the buttons to zoom out to view the entire protein, to highlight the four pore helices that point their negative ends towards the ion, and to highlight the small intramembrane loop that partially blocks the pore and may be important


  1. Han, G. W. et al. Structure of a tryptophanyl-tRNA synthetase containing an iron-sulfur cluster. Acta Cryst. F66, 1326-1334 (2010).
    Shen, N., Guo, L., Jin, Y. & Ding, J. Structure of human tryptophanyl-tRNA synthetase in complex with tRNAtrp reveals the molecular basis of tRNA recognition and specificity. Nucl. Acids Res. 34, 3246-3258 (2006).

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health