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PDBsum entry 1kmm

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protein ligands Protein-protein interface(s) links
Aminoacyl-tRNA synthase PDB id
1kmm
Jmol
Contents
Protein chains
386 a.a. *
364 a.a. *
Ligands
HAM ×4
Waters ×184
* Residue conservation analysis
PDB id:
1kmm
Name: Aminoacyl-tRNA synthase
Title: Histidyl-tRNA synthetase complexed with histidyl-adenylate
Structure: Histidyl-tRNA synthetase. Chain: a, b, c, d. Synonym: histidine-tRNA ligase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Strain: jm109. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: trp-lac. Other_details: induction with iptg
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
2.60Å     R-factor:   0.221     R-free:   0.297
Authors: J.G.Arnez,C.S.Francklyn,D.Moras
Key ref:
J.G.Arnez et al. (1997). The first step of aminoacylation at the atomic level in histidyl-tRNA synthetase. Proc Natl Acad Sci U S A, 94, 7144-7149. PubMed id: 9207058 DOI: 10.1073/pnas.94.14.7144
Date:
09-May-97     Release date:   17-Dec-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P60906  (SYH_ECOLI) -  Histidine--tRNA ligase
Seq:
Struc:
424 a.a.
386 a.a.
Protein chains
Pfam   ArchSchema ?
P60906  (SYH_ECOLI) -  Histidine--tRNA ligase
Seq:
Struc:
424 a.a.
364 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.6.1.1.21  - Histidine--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-histidine + tRNA(His) = AMP + diphosphate + L-histidyl-tRNA(His)
ATP
+ L-histidine
+ tRNA(His)
=
AMP
Bound ligand (Het Group name = HAM)
matches with 69.00% similarity
+ diphosphate
+ L-histidyl-tRNA(His)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     translation   3 terms 
  Biochemical function     nucleotide binding     5 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.94.14.7144 Proc Natl Acad Sci U S A 94:7144-7149 (1997)
PubMed id: 9207058  
 
 
The first step of aminoacylation at the atomic level in histidyl-tRNA synthetase.
J.G.Arnez, J.G.Augustine, D.Moras, C.S.Francklyn.
 
  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.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Stereoviews of superpositions of the histidinol:ATP (blue bonds) and histidyl-adenylate (red bonds) complexes (a), and the^ ATPs from the HisRS:histidinol:ATP complex (red) and yeast AspRS:tRNA:ATP complex (blue) (b). The figure was prepared by using MOLSCRIPT (27) and RASTER3D (28, 29).
Figure 2.
Fig. 2. Stereoviews of electron density maps of ligands in the active site of HisRS. Final 2F[o] F[c] map contoured at 1 of the active^ site of the HisRS:HisOH:ATP complex (a) and HisRS:HisAMP complex (b), superposed on the final refined structures. (c) HisRS:HisOH:ATP:Mn2+ complex. An F[o] F[c] map contoured at 4.5 (red); the map was computed with structure factors and phases calculated from the^ model in a. The figure was prepared by using MINIMAGE (30), MOLSCRIPT (27), and RASTER3D (28, 29).
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21464306 S.B.Pierce, K.M.Chisholm, E.D.Lynch, M.K.Lee, T.Walsh, J.M.Opitz, W.Li, R.E.Klevit, and M.C.King (2011).
Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome.
  Proc Natl Acad Sci U S A, 108, 6543-6548.  
20132829 E.A.Merritt, T.L.Arakaki, J.R.Gillespie, E.T.Larson, A.Kelley, N.Mueller, A.J.Napuli, J.Kim, L.Zhang, C.L.Verlinde, E.Fan, F.Zucker, F.S.Buckner, W.C.van Voorhis, and W.G.Hol (2010).
Crystal structures of trypanosomal histidyl-tRNA synthetase illuminate differences between eukaryotic and prokaryotic homologs.
  J Mol Biol, 397, 481-494.
PDB codes: 3hri 3hrk 3lc0
19487703 E.Guth, M.Farris, M.Bovee, and C.S.Francklyn (2009).
Asymmetric amino acid activation by class II histidyl-tRNA synthetase from Escherichia coli.
  J Biol Chem, 284, 20753-20762.  
19505149 F.Fan, and J.S.Blanchard (2009).
Toward the catalytic mechanism of a cysteine ligase (MshC) from Mycobacterium smegmatis: an enzyme involved in the biosynthetic pathway of mycothiol.
  Biochemistry, 48, 7150-7159.  
18850722 C.S.Francklyn (2008).
DNA polymerases and aminoacyl-tRNA synthetases: shared mechanisms for ensuring the fidelity of gene expression.
  Biochemistry, 47, 11695-11703.  
17317626 E.C.Guth, and C.S.Francklyn (2007).
Kinetic discrimination of tRNA identity by the conserved motif 2 loop of a class II aminoacyl-tRNA synthetase.
  Mol Cell, 25, 531-542.  
17428498 P.Retailleau, V.Weinreb, M.Hu, and C.W.Carter (2007).
Crystal structure of tryptophanyl-tRNA synthetase complexed with adenosine-5' tetraphosphate: evidence for distributed use of catalytic binding energy in amino acid activation by class I aminoacyl-tRNA synthetases.
  J Mol Biol, 369, 108-128.
PDB code: 2ov4
15657145 M.A.Swairjo, and P.R.Schimmel (2005).
Breaking sieve for steric exclusion of a noncognate amino acid from active site of a tRNA synthetase.
  Proc Natl Acad Sci U S A, 102, 988-993.
PDB codes: 1yfr 1yfs 1yft 1ygb
15595717 P.S.Pang, E.Jankowsky, L.M.Wadley, and A.M.Pyle (2005).
Prediction of functional tertiary interactions and intermolecular interfaces from primary sequence data.
  J Exp Zoolog B Mol Dev Evol, 304, 50-63.  
14690420 M.L.Bovee, M.A.Pierce, and C.S.Francklyn (2003).
Induced fit and kinetic mechanism of adenylation catalyzed by Escherichia coli threonyl-tRNA synthetase.
  Biochemistry, 42, 15102-15113.  
11679717 R.Fishman, V.Ankilova, N.Moor, and M.Safro (2001).
Structure at 2.6 A resolution of phenylalanyl-tRNA synthetase complexed with phenylalanyl-adenylate in the presence of manganese.
  Acta Crystallogr D Biol Crystallogr, 57, 1534-1544.
PDB code: 1jjc
11329259 S.A.Hawko, and C.S.Francklyn (2001).
Covariation of a specificity-determining structural motif in an aminoacyl-tRNA synthetase and a tRNA identity element.
  Biochemistry, 40, 1930-1936.  
10913247 G.Desogus, F.Todone, P.Brick, and S.Onesti (2000).
Active site of lysyl-tRNA synthetase: structural studies of the adenylation reaction.
  Biochemistry, 39, 8418-8425.
PDB codes: 1e1o 1e1t 1e22 1e24
10713991 K.A.Denessiouk, and M.S.Johnson (2000).
When fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.
  Proteins, 38, 310-326.  
10966471 M.Ibba, and D.Soll (2000).
Aminoacyl-tRNA synthesis.
  Annu Rev Biochem, 69, 617-650.  
11041850 S.Onesti, G.Desogus, A.Brevet, J.Chen, P.Plateau, S.Blanquet, and P.Brick (2000).
Structural studies of lysyl-tRNA synthetase: conformational changes induced by substrate binding.
  Biochemistry, 39, 12853-12861.
PDB codes: 1bbu 1bbw
10504407 J.J.Berlanga, J.Santoyo, and C.De Haro (1999).
Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase.
  Eur J Biochem, 265, 754-762.  
10430882 M.Sissler, C.Delorme, J.Bond, S.D.Ehrlich, P.Renault, and C.Francklyn (1999).
An aminoacyl-tRNA synthetase paralog with a catalytic role in histidine biosynthesis.
  Proc Natl Acad Sci U S A, 96, 8985-8990.  
10430027 W.Freist, J.F.Verhey, A.Rühlmann, D.H.Gauss, and J.G.Arnez (1999).
Histidyl-tRNA synthetase.
  Biol Chem, 380, 623-646.  
9582288 C.Berthet-Colominas, L.Seignovert, M.Härtlein, M.Grotli, S.Cusack, and R.Leberman (1998).
The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate: the mechanism of discrimination between asparagine and aspartic acid.
  EMBO J, 17, 2947-2960.  
9724658 E.Schmitt, L.Moulinier, S.Fujiwara, T.Imanaka, J.C.Thierry, and D.Moras (1998).
Crystal structure of aspartyl-tRNA synthetase from Pyrococcus kodakaraensis KOD: archaeon specificity and catalytic mechanism of adenylate formation.
  EMBO J, 17, 5227-5237.
PDB codes: 1b8a 3nel 3nem 3nen
9753692 M.Rizzi, M.Bolognesi, and A.Coda (1998).
A novel deamido-NAD+-binding site revealed by the trapped NAD-adenylate intermediate in the NAD+ synthetase structure.
  Structure, 6, 1129-1140.
PDB code: 2nsy
9434910 S.Cusack (1997).
Aminoacyl-tRNA synthetases.
  Curr Opin Struct Biol, 7, 881-889.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.