Home LiteratureArticle Details
PMID: 9207058 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The first step of aminoacylation at the atomic level in histidyl-tRNA synthetase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 14 ·1997-07-08 ·Pages 7144-9

Arnez JG, Augustine JG, Moras D, Francklyn CS

Abstract

The crystal structure of an enzyme-substrate complex with histidyl-tRNA synthetase from Escherichia coli, ATP, and the amino acid analog histidinol is described and compared with the previously obtained enzyme-product complex with histidyl-adenylate. An active site arginine, Arg-259, unique to all histidyl-tRNA synthetases, plays the role of the catalytic magnesium ion seen in seryl-tRNA synthetase. When Arg-259 is substituted with histidine, the apparent second order rate constant (kcat/Km) for the pyrophosphate exchange reaction and the aminoacylation reaction decreases 1,000-fold and 500-fold, respectively. Crystals soaked with MnCl2 reveal the existence of two metal binding sites between beta- and gamma-phosphates; these sites appear to stabilize the conformation of the pyrophosphate. The use of both conserved metal ions and arginine in phosphoryl transfer provides evidence of significant early functional divergence of class II aminoacyl-tRNA synthetases.

MeSH Terms
Acylation Crystallization Escherichia coli Histidine-tRNA Ligase/chemistry,genetics Kinetics Molecular Sequence Data Mutagenesis, Site-Directed
Chemicals
Histidine-tRNA Ligase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Arnez J G
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, BP 163, 67404 Strasbourg-Illkirch, Cedex, France.
Augustine J G
Moras D
Francklyn C S
References (36)
36 references, click to expand
  1. Structural and functional relationships between aminoacyl-tRNA synthetases.
    Trends Biochem Sci. 1992 Apr;17(4):159-64 PMID: 1585461
  2. Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis.
    J Mol Biol. 1991 Mar 20;218(2):449-64 PMID: 2010919
  3. Eleven down and nine to go.
    Nat Struct Biol. 1995 Oct;2(10):824-31 PMID: 7552701
  4. A tRNA identity switch mediated by the binding interaction between a tRNA anticodon and the accessory domain of a class II aminoacyl-tRNA synthetase.
    Biochemistry. 1996 May 28;35(21):6559-68 PMID: 8639604
  5. Rapid and efficient site-specific mutagenesis without phenotypic selection.
    Methods Enzymol. 1987;154:367-82 PMID: 3323813
  6. The crystal structure of the lysyl-tRNA synthetase (LysU) from Escherichia coli.
    Structure. 1995 Feb 15;3(2):163-76 PMID: 7735833
  7. Structure of tyrosyl-tRNA synthetase refined at 2.3 A resolution. Interaction of the enzyme with the tyrosyl adenylate intermediate.
    J Mol Biol. 1989 Jul 5;208(1):83-98 PMID: 2504923
  8. Crystallographic study at 2.5 A resolution of the interaction of methionyl-tRNA synthetase from Escherichia coli with ATP.
    J Mol Biol. 1990 Nov 20;216(2):411-24 PMID: 2254937
  9. Crystal structure of histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate.
    EMBO J. 1995 Sep 1;14(17):4143-55 PMID: 7556055
  10. Improved methods for building protein models in electron density maps and the location of errors in these models.
    Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 PMID: 2025413
  11. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs.
    Nature. 1990 Sep 13;347(6289):203-6 PMID: 2203971
  12. Staphylococcal nuclease: proposed mechanism of action based on structure of enzyme-thymidine 3',5'-bisphosphate-calcium ion complex at 1.5-A resolution.
    Proc Natl Acad Sci U S A. 1979 Jun;76(6):2551-5 PMID: 288045
  13. Role of divalent metal ions in the hammerhead RNA cleavage reaction.
    Biochemistry. 1991 Oct 1;30(39):9464-9 PMID: 1716459
  14. Torsion angle dynamics: reduced variable conformational sampling enhances crystallographic structure refinement.
    Proteins. 1994 Aug;19(4):277-90 PMID: 7984624
  15. Structure of E. coli glutaminyl-tRNA synthetase complexed with tRNA(Gln) and ATP at 2.8 A resolution.
    Science. 1989 Dec 1;246(4934):1135-42 PMID: 2479982
  16. The catalytic properties of tyrosyl ribonucleic acid synthetases from Escherichia coli and Bacillus subtilis.
    Biochemistry. 1966 May;5(5):1690-5 PMID: 4289778
  17. Metal ion catalysis in the Tetrahymena ribozyme reaction.
    Nature. 1993 Jan 7;361(6407):85-8 PMID: 8421499
  18. Tryptophanyl-tRNA synthetase crystal structure reveals an unexpected homology to tyrosyl-tRNA synthetase.
    Structure. 1995 Jan 15;3(1):17-31 PMID: 7743129
  19. A general two-metal-ion mechanism for catalytic RNA.
    Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6498-502 PMID: 8341661
  20. The active site of yeast aspartyl-tRNA synthetase: structural and functional aspects of the aminoacylation reaction.
    EMBO J. 1994 Jan 15;13(2):327-37 PMID: 8313877
  21. Cognition, mechanism, and evolutionary relationships in aminoacyl-tRNA synthetases.
    Annu Rev Biochem. 1993;62:715-48 PMID: 8352600
  22. Raster3D Version 2.0. A program for photorealistic molecular graphics.
    Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):869-73 PMID: 15299354
  23. Enzyme-catalyzed phosphoryl transfer reactions.
    Annu Rev Biochem. 1980;49:877-919 PMID: 6250450
  24. Configurationally defined phosphorothioate-containing oligoribonucleotides in the study of the mechanism of cleavage of hammerhead ribozymes.
    Nucleic Acids Res. 1991 Mar 25;19(6):1183-8 PMID: 1709484
  25. The structural basis for seryl-adenylate and Ap4A synthesis by seryl-tRNA synthetase.
    Structure. 1995 Apr 15;3(4):341-52 PMID: 7613865
  26. Synthesis and recognition of aspartyl-adenylate by Thermus thermophilus aspartyl-tRNA synthetase.
    J Mol Biol. 1994 Nov 25;244(2):158-67 PMID: 7966328
  27. Multiple magnesium ions in the ribonuclease P reaction mechanism.
    Biochemistry. 1993 May 25;32(20):5273-81 PMID: 8499432
  28. Cocrystal structure of an editing complex of Klenow fragment with DNA.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8924-8 PMID: 3194400
  29. Aminoacyl-RNA synthesis catalyzed by an RNA.
    Science. 1995 Feb 3;267(5198):643-7 PMID: 7530860
  30. The stereochemical course of amino acid activation by methionyl- and tyrosyl-tRNA synthetases.
    Nature. 1979 Sep 27;281(5729):320-1 PMID: 399325
  31. Effects of phosphorothioate and 2-amino groups in hammerhead ribozymes on cleavage rates and Mg2+ binding.
    Biochemistry. 1991 May 28;30(21):5145-50 PMID: 2036380
  32. Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate.
    Science. 1994 Mar 11;263(5152):1432-6 PMID: 8128224
  33. Crystal structure of the rat liver fructose-2,6-bisphosphatase based on selenomethionine multiwavelength anomalous dispersion phases.
    Biochemistry. 1996 May 14;35(19):6010-9 PMID: 8634242
  34. Crystallization of histidyl-tRNA synthetase from Escherichia coli.
    J Mol Biol. 1994 Aug 12;241(2):275-7 PMID: 8057367
  35. Structural basis for the 3'-5' exonuclease activity of Escherichia coli DNA polymerase I: a two metal ion mechanism.
    EMBO J. 1991 Jan;10(1):25-33 PMID: 1989886
  36. Histidyl-tRNA synthetase from Salmonella typhimurium: specificity in the binding of histidine analogues.
    Eur J Biochem. 1975 Aug 15;56(2):369-74 PMID: 1100392
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.14.7144
Published
1997-07-08
Pages
7144-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23771
Subset
IM
Grants
NIGMS NIH HHS · R01 GM054899 · United States
NIGMS NIH HHS · GM 48146 · United States
Databases
PDB
1KMM, 1KMN
External Links
PubMed source DOI: 10.1073/pnas.94.14.7144 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2