2ag6 › Citations

Structural plasticity of an aminoacyl-tRNA synthetase active site.

Turner JM, Graziano J, Spraggon G, Schultz PG
Proc Natl Acad Sci U S A 103 6483-8 (2006)
Cited: 36 times
EuropePMC logo PMID: 16618920

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.

Articles - 2ag6 mentioned but not cited (6)

  1. Continuous directed evolution of aminoacyl-tRNA synthetases. Bryson DI, Fan C, Guo LT, Miller C, Söll D, Liu DR. Nat Chem Biol 13 1253-1260 (2017)
  2. Structural plasticity of an aminoacyl-tRNA synthetase active site. Turner JM, Graziano J, Spraggon G, Schultz PG. Proc Natl Acad Sci U S A 103 6483-6488 (2006)
  3. Overcoming Near-Cognate Suppression in a Release Factor 1-Deficient Host with an Improved Nitro-Tyrosine tRNA Synthetase. Beyer JN, Hosseinzadeh P, Gottfried-Lee I, Van Fossen EM, Zhu P, Bednar RM, Karplus PA, Mehl RA, Cooley RB. J Mol Biol 432 4690-4704 (2020)
  4. Improved Modeling of Halogenated Ligand-Protein Interactions Using the Drude Polarizable and CHARMM Additive Empirical Force Fields. Lin FY, MacKerell AD. J Chem Inf Model 59 215-228 (2019)
  5. Engineering aminoacyl-tRNA synthetases for use in synthetic biology. Krahn N, Tharp JM, Crnković A, Söll D. Enzymes 48 351-395 (2020)
  6. Development and Testing of Force Field Parameters for Phenylalanine and Tyrosine Derivatives. Wang X, Li W. Front Mol Biosci 7 608931 (2020)


Reviews citing this publication (6)

  1. Adding new chemistries to the genetic code. Liu CC, Schultz PG. Annu Rev Biochem 79 413-444 (2010)
  2. Enzyme promiscuity: a mechanistic and evolutionary perspective. Khersonsky O, Tawfik DS. Annu Rev Biochem 79 471-505 (2010)
  3. Designing logical codon reassignment - Expanding the chemistry in biology. Dumas A, Lercher L, Spicer CD, Davis BG. Chem Sci 6 50-69 (2015)
  4. Beyond the canonical 20 amino acids: expanding the genetic lexicon. Young TS, Schultz PG. J Biol Chem 285 11039-11044 (2010)
  5. Playing with the Molecules of Life. Young DD, Schultz PG. ACS Chem Biol 13 854-870 (2018)
  6. Synthesis at the interface of chemistry and biology. Wu X, Schultz PG. J Am Chem Soc 131 12497-12515 (2009)

Articles citing this publication (24)

  1. An enhanced system for unnatural amino acid mutagenesis in E. coli. Young TS, Ahmad I, Yin JA, Schultz PG. J Mol Biol 395 361-374 (2010)
  2. Crystal structure of an ancient protein: evolution by conformational epistasis. Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW. Science 317 1544-1548 (2007)
  3. Genetic incorporation of unnatural amino acids into proteins in mammalian cells. Liu W, Brock A, Chen S, Chen S, Schultz PG. Nat Methods 4 239-244 (2007)
  4. A chemical toolkit for proteins--an expanded genetic code. Xie J, Schultz PG. Nat Rev Mol Cell Biol 7 775-782 (2006)
  5. An evolved aminoacyl-tRNA synthetase with atypical polysubstrate specificity. Young DD, Young TS, Jahnz M, Ahmad I, Spraggon G, Schultz PG. Biochemistry 50 1894-1900 (2011)
  6. Stereochemical basis for engineered pyrrolysyl-tRNA synthetase and the efficient in vivo incorporation of structurally divergent non-native amino acids. Takimoto JK, Dellas N, Noel JP, Wang L. ACS Chem Biol 6 733-743 (2011)
  7. A genetically encoded bidentate, metal-binding amino acid. Xie J, Liu W, Schultz PG. Angew Chem Int Ed Engl 46 9239-9242 (2007)
  8. A genetically encoded diazirine photocrosslinker in Escherichia coli. Tippmann EM, Liu W, Summerer D, Mack AV, Schultz PG. Chembiochem 8 2210-2214 (2007)
  9. Genetic incorporation of twelve meta-substituted phenylalanine derivatives using a single pyrrolysyl-tRNA synthetase mutant. Wang YS, Fang X, Chen HY, Wu B, Wang ZU, Hilty C, Liu WR. ACS Chem Biol 8 405-415 (2013)
  10. Genetic encoding of 3-iodo-L-tyrosine in Escherichia coli for single-wavelength anomalous dispersion phasing in protein crystallography. Sakamoto K, Murayama K, Oki K, Iraha F, Kato-Murayama M, Takahashi M, Ohtake K, Kobayashi T, Kuramitsu S, Shirouzu M, Yokoyama S. Structure 17 335-344 (2009)
  11. Letter Expanding the genetic code of Escherichia coli with phosphotyrosine. Fan C, Ip K, Söll D. FEBS Lett 590 3040-3047 (2016)
  12. Structural basis of improved second-generation 3-nitro-tyrosine tRNA synthetases. Cooley RB, Feldman JL, Driggers CM, Bundy TA, Stokes AL, Karplus PA, Mehl RA. Biochemistry 53 1916-1924 (2014)
  13. Enhancing the utility of unnatural amino acid synthetases by manipulating broad substrate specificity. Stokes AL, Miyake-Stoner SJ, Peeler JC, Nguyen DP, Hammer RP, Mehl RA. Mol Biosyst 5 1032-1038 (2009)
  14. A critical examination of Escherichia coli esterase activity. Antonczak AK, Simova Z, Tippmann EM. J Biol Chem 284 28795-28800 (2009)
  15. Structure-guided directed evolution of highly selective p450-based magnetic resonance imaging sensors for dopamine and serotonin. Brustad EM, Lelyveld VS, Snow CD, Crook N, Jung ST, Martinez FM, Scholl TJ, Jasanoff A, Arnold FH. J Mol Biol 422 245-262 (2012)
  16. Gleaning unexpected fruits from hard-won synthetases: probing principles of permissivity in non-canonical amino acid-tRNA synthetases. Cooley RB, Karplus PA, Mehl RA. Chembiochem 15 1810-1819 (2014)
  17. Structural basis for the recognition of para-benzoyl-L-phenylalanine by evolved aminoacyl-tRNA synthetases. Liu W, Alfonta L, Mack AV, Schultz PG. Angew Chem Int Ed Engl 46 6073-6075 (2007)
  18. Improved Incorporation of Noncanonical Amino Acids by an Engineered tRNA(Tyr) Suppressor. Rauch BJ, Porter JJ, Mehl RA, Perona JJ. Biochemistry 55 618-628 (2016)
  19. Distributions of enzyme residues yielding mutants with improved substrate specificities from two different directed evolution strategies. Paramesvaran J, Hibbert EG, Russell AJ, Dalby PA. Protein Eng Des Sel 22 401-411 (2009)
  20. Novel chloroquine loaded curcumin based anionic linear globular dendrimer G2: a metabolomics study on Plasmodium falciparum in vitro using 1H NMR spectroscopy. Elmi T, Shafiee Ardestani M, Hajialiani F, Motevalian M, Mohamadi M, Sadeghi S, Zamani Z, Tabatabaie F. Parasitology 147 747-759 (2020)
  21. Replacement of Y730 and Y731 in the alpha2 subunit of Escherichia coli ribonucleotide reductase with 3-aminotyrosine using an evolved suppressor tRNA/tRNA-synthetase pair. Seyedsayamdost MR, Stubbe J. Methods Enzymol 462 45-76 (2009)
  22. Site-specific incorporation of unnatural amino acids into urate oxidase in Escherichia coli. Chen M, Cai L, Fang Z, Tian H, Gao X, Yao W. Protein Sci 17 1827-1833 (2008)
  23. The juggernauts of biology. Yonemoto IT, Tippmann EM. Bioessays 32 314-321 (2010)
  24. Crystal Structure of an Archaeal Tyrosyl-tRNA Synthetase Bound to Photocaged L-Tyrosine and Its Potential Application to Time-Resolved X-ray Crystallography. Hosaka T, Katsura K, Ishizuka-Katsura Y, Hanada K, Ito K, Tomabechi Y, Inoue M, Akasaka R, Takemoto C, Shirouzu M. Int J Mol Sci 23 10399 (2022)


Quick links