Structural plasticity of an aminoacyl-tRNA synthetase active site.

Abstract:

:Recently, tRNA aminoacyl-tRNA synthetase pairs have been evolved that allow one to genetically encode a large array of unnatural amino acids in both prokaryotic and eukaryotic organisms. We have determined the crystal structures of two substrate-bound Methanococcus jannaschii tyrosyl aminoacyl-tRNA synthetases that charge the unnatural amino acids p-bromophenylalanine and 3-(2-naphthyl)alanine (NpAla). A comparison of these structures with the substrate-bound WT synthetase, as well as a mutant synthetase that charges p-acetylphenylalanine, shows that altered specificity is due to both side-chain and backbone rearrangements within the active site that modify hydrogen bonds and packing interactions with substrate, as well as disrupt the alpha8-helix, which spans the WT active site. The high degree of structural plasticity that is observed in these aminoacyl-tRNA synthetases is rarely found in other mutant enzymes with altered specificities and provides an explanation for the surprising adaptability of the genetic code to novel amino acids.

authors

Turner JM,Graziano J,Spraggon G,Schultz PG

doi

10.1073/pnas.0601756103

subject

Has Abstract

pub_date

2006-04-25 00:00:00

pages

6483-8

issue

17

eissn

0027-8424

issn

1091-6490

pii

0601756103

journal_volume

103

pub_type

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