3QE4

An evolved aminoacyl-tRNA Synthetase with atypical polysubstrate specificity

Summary for 3QE4

• Entry DOI: 10.2210/pdb3qe4/pdb
• Related: 1ZH0 1ZH6 2AG6
• Descriptor: Tyrosyl-tRNA synthetase, 4-cyano-L-phenylalanine (3 entities in total)
• Functional Keywords: evolved trna synthetase, trna synthetase evolved to bind unnatural amino acids, trna, ligase
• Biological source: Methanocaldococcus jannaschii (Methanococcus jannaschii)
• Cellular location: Cytoplasm: Q57834
• Total number of polymer chains: 2
• Total formula weight: 71908.01

Authors

Young, D.D.,Young, T.S.,Jahnz, M.,Ahmad, I.,Spraggon, G.,Schultz, P.G. (deposition date: 2011-01-19, release date: 2011-02-16, Last modification date: 2023-12-06)

Primary citation

Young, D.D.,Young, T.S.,Jahnz, M.,Ahmad, I.,Spraggon, G.,Schultz, P.G.
An Evolved Aminoacyl-tRNA Synthetase with Atypical Polysubstrate Specificity .
Biochemistry, 50:1894-1900, 2011

PubMed Abstract: We have employed a rapid fluorescence-based screen to assess the polyspecificity of several aminoacyl-tRNA synthetases (aaRSs) against an array of unnatural amino acids. We discovered that a p-cyanophenylalanine specific aminoacyl-tRNA synthetase (pCNF-RS) has high substrate permissivity for unnatural amino acids, while maintaining its ability to discriminate against the 20 canonical amino acids. This orthogonal pCNF-RS, together with its cognate amber nonsense suppressor tRNA, is able to selectively incorporate 18 unnatural amino acids into proteins, including trifluoroketone-, alkynyl-, and halogen-substituted amino acids. In an attempt to improve our understanding of this polyspecificity, the X-ray crystal structure of the aaRS-p-cyanophenylalanine complex was determined. A comparison of this structure with those of other mutant aaRSs showed that both binding site size and other more subtle features control substrate polyspecificity.

PubMed: 21280675
DOI: 10.1021/bi101929e

Experimental method

X-RAY DIFFRACTION (2.3 Å)