Structural plasticity of an aminoacyl-tRNA synthetase active site.

Proceedings of the National Academy of Sciences of the United States of America
James M TurnerPeter G Schultz

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.

References

Mar 1, 1991·Molecular Microbiology·A BöckF Zinoni
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Jun 17, 1988·Science·L G Presta, G D Rose
Jun 17, 1988·Science·J S Richardson, D C Richardson
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·R ChenA M Dean
Jun 13, 1997·Science·G J WedemayerR C Stevens
Apr 1, 1997·Journal of Molecular Graphics & Modelling·R M Esnouf
Apr 21, 2001·Science·L WangP G Schultz
Feb 28, 2002·Journal of the American Chemical Society·Lei WangPeter G Schultz
May 25, 2002·Science·Gayathri SrinivasanJoseph A Krzycki
Aug 1, 2002·Journal of the American Chemical Society·Jason W ChinPeter G Schultz
Aug 3, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jason W ChinPeter G Schultz
Jan 9, 2003·Proceedings of the National Academy of Sciences of the United States of America·Lei WangPeter G Schultz
Feb 13, 2003·Journal of Molecular Biology·Matthew H J CordesRobert T Sauer
May 20, 2003·Nature Structural Biology·Takatsugu KobayashiShigeyuki Yokoyama
Jul 10, 2003·Journal of Molecular Biology·Jun YinPeter G Schultz
Jan 17, 2004·Science·Zhiwen ZhangPeter G Schultz
Nov 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·E A Merritt, M E Murphy
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jan 1, 1993·Acta Crystallographica. Section D, Biological Crystallography·V S Lamzin, K S Wilson
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Carla PolycarpoDieter Söll
Dec 16, 2004·Angewandte Chemie·Lei Wang, Peter G Schultz
Jan 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Takatsugu KobayashiShigeyuki Yokoyama
Feb 22, 2005·Nature Structural & Molecular Biology·Madhavan R Buddha, Brian R Crane
Oct 27, 2005·Journal of the American Chemical Society·James M TurnerPeter G Schultz
May 13, 2006·Annual Review of Biophysics and Biomolecular Structure·Lei WangPeter G Schultz
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Feb 2, 2011·Biochemistry·Douglas D YoungPeter G Schultz
Feb 27, 2007·Nature Methods·Wenshe LiuPeter G Schultz
Aug 24, 2006·Nature Reviews. Molecular Cell Biology·Jianming Xie, Peter G Schultz
Aug 12, 2009·The Journal of Biological Chemistry·Alicja K AntonczakEric M Tippmann
Feb 12, 2010·The Journal of Biological Chemistry·Travis S Young, Peter G Schultz
Jun 9, 2009·Protein Engineering, Design & Selection : PEDS·Janahan ParamesvaranPaul A Dalby
Aug 19, 2007·Science·Eric A OrtlundJoseph W Thornton
Mar 20, 2010·Annual Review of Biochemistry·Olga Khersonsky, Dan S Tawfik
Mar 24, 2010·Annual Review of Biochemistry·Chang C Liu, Peter G Schultz
Dec 24, 2015·Biochemistry·Benjamin Julius RauchJohn J Perona
Oct 27, 2009·Journal of Molecular Biology·Travis S YoungPeter G Schultz
Jul 4, 2008·Protein Science : a Publication of the Protein Society·Mingjie ChenWenbing Yao
Mar 11, 2010·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Isaac T Yonemoto, Eric M Tippmann
Aug 2, 2016·FEBS Letters·Chenguang FanDieter Söll
Jul 22, 2014·Chembiochem : a European Journal of Chemical Biology·Richard B CooleyRyan A Mehl
Mar 13, 2014·Biochemistry·Richard B CooleyRyan A Mehl
Oct 17, 2017·Nature Chemical Biology·David I BrysonDavid R Liu
Jan 1, 2015·Chemical Science·Anaëlle DumasBenjamin G Davis
Sep 26, 2007·Angewandte Chemie·Jianming XiePeter G Schultz
Nov 15, 2007·Chembiochem : a European Journal of Chemical Biology·Eric M TippmannPeter G Schultz
Feb 23, 2020·Annual Review of Biophysics·Paul CampitelliS Banu Ozkan
Jan 2, 2021·Frontiers in Molecular Biosciences·Xiaowen Wang, Wenjin Li
Dec 14, 2006·ACS Chemical Biology·Sandro F Ataide, Michael Ibba
Aug 20, 2009·Journal of the American Chemical Society·Xu Wu, Peter G Schultz
Jan 20, 2010·Biochemistry·Shigeki J Miyake-StonerRyan A Mehl
Jan 19, 2018·ACS Chemical Biology·Douglas D Young, Peter G Schultz
Nov 13, 2018·Journal of Chemical Information and Modeling·Fang-Yu Lin, Alexander D MacKerell
Oct 19, 2012·Biochemistry·John J Perona, Andrew Hadd
Oct 1, 2013·Bioconjugate Chemistry·Shuo Chen, Meng-Lin Tsao

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