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PDBsum entry 1jzq

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protein ligands metals links
Ligase PDB id
1jzq
Jmol
Contents
Protein chain
821 a.a. *
Ligands
ILA
Metals
_ZN ×2
* Residue conservation analysis
PDB id:
1jzq
Name: Ligase
Title: Isoleucyl-tRNA synthetase complexed with isoleucyl- adenylate analogue
Structure: Isoleucyl-tRNA synthetase. Chain: a. Engineered: yes
Source: Thermus thermophilus. Organism_taxid: 274. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
3.00Å     R-factor:   0.220     R-free:   0.272
Authors: T.Nakama,O.Nureki,S.Yokoyama,Riken Structural Genomics/proteomics Initiative (Rsgi)
Key ref:
T.Nakama et al. (2001). Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase. J Biol Chem, 276, 47387-47393. PubMed id: 11584022 DOI: 10.1074/jbc.M109089200
Date:
17-Sep-01     Release date:   21-Dec-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P56690  (SYI_THET8) -  Isoleucine--tRNA ligase
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1043 a.a.
821 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.6.1.1.5  - Isoleucine--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-isoleucyl- tRNA(Ile)
ATP
+ L-isoleucine
+ tRNA(Ile)
=
AMP
Bound ligand (Het Group name = ILA)
matches with 50.00% similarity
+ diphosphate
+ L-isoleucyl- tRNA(Ile)
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     tRNA aminoacylation for protein translation   2 terms 
  Biochemical function     aminoacyl-tRNA editing activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M109089200 J Biol Chem 276:47387-47393 (2001)
PubMed id: 11584022  
 
 
Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase.
T.Nakama, O.Nureki, S.Yokoyama.
 
  ABSTRACT  
 
An analogue of isoleucyl-adenylate (Ile-AMS) potently inhibits the isoleucyl-tRNA synthetases (IleRSs) from the three primary kingdoms, whereas the antibiotic mupirocin inhibits only the eubacterial and archaeal IleRSs, but not the eukaryotic enzymes, and therefore is clinically used against methicillin-resistant Staphylococcus aureus. We determined the crystal structures of the IleRS from the thermophilic eubacterium, Thermus thermophilus, in complexes with Ile-AMS and mupirocin at 3.0- and 2.5-A resolutions, respectively. A structural comparison of the IleRS.Ile-AMS complex with the adenylate complexes of other aminoacyl-tRNA synthetases revealed the common recognition mode of aminoacyl-adenylate by the class I aminoacyl-tRNA synthetases. The Ile-AMS and mupirocin, which have significantly different chemical structures, are recognized by many of the same amino acid residues of the IleRS, suggesting that the antibiotic inhibits the enzymatic activity by blocking the binding site of the high energy intermediate, Ile-AMP. In contrast, the two amino acid residues that concomitantly recognize Ile-AMS and mupirocin are different between the eubacterial/archaeal IleRSs and the eukaryotic IleRSs. Mutagenic analyses revealed that the replacement of the two residues significantly changed the sensitivity to mupirocin.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Chemical structures of Ile-AMP , Ile-AMS, and mupirocin (pseudomonic acid A) (14).
Figure 2.
Fig. 2. a, omit electron density, contoured at 3.5 , for the Ile-AMS molecule bound to the IleRS. b, crystal structure of the complex of T. thermophilus IleRS with Ile-AMS. The N-terminal and C-terminal halves of the Rossmann fold domain are colored in orange and yellow, respectively. The bound Ile-AMP molecule is shown by a blue CPK model. c, Ile-AMS molecule bound to the catalytic site of the IleRS. The Ile-AMS molecule is shown in green. The amino acid residues that recognize Ile-AMS are indicated by ball-and-stick models. d, schematic drawing of the hydrogen bond between the Ile-AMS and the IleRS. The side chain of the isoleucyl moiety, the -NH and -CO of the isoleucyl moiety, the phosphate analogue moiety, the ribose moiety, and the adenine moiety of Ile-AMS are colored in red, yellow, green, blue, and violet, respectively.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 47387-47393) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23263184 H.Zhou, L.Sun, X.L.Yang, and P.Schimmel (2013).
ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase.
  Nature, 494, 121-124.
PDB code: 4hvc
21205898 E.S.Istvan, N.V.Dharia, S.E.Bopp, I.Gluzman, E.A.Winzeler, and D.E.Goldberg (2011).
Validation of isoleucine utilization targets in Plasmodium falciparum.
  Proc Natl Acad Sci U S A, 108, 1627-1632.  
21392992 M.T.Gutierrez-Lugo, and C.A.Bewley (2011).
Susceptibility and mode of binding of the Mycobacterium tuberculosis cysteinyl transferase mycothiol ligase to tRNA synthetase inhibitors.
  Bioorg Med Chem Lett, 21, 2480-2483.  
21336932 R.Gurney, and C.M.Thomas (2011).
Mupirocin: biosynthesis, special features and applications of an antibiotic from a Gram-negative bacterium.
  Appl Microbiol Biotechnol, 90, 11-21.  
20190824 C.M.Thomas, J.Hothersall, C.L.Willis, and T.J.Simpson (2010).
Resistance to and synthesis of the antibiotic mupirocin.
  Nat Rev Microbiol, 8, 281-289.  
21127037 G.Kawai, and S.Yokoyama (2010).
Professor Tatsuo Miyazawa: from molecular structure to biological function.
  J Biochem, 148, 631-638.  
20796028 H.Ingvarsson, and T.Unge (2010).
Flexibility and communication within the structure of the Mycobacterium smegmatis methionyl-tRNA synthetase.
  FEBS J, 277, 3947-3962.
PDB codes: 2x1l 2x1m
20123733 M.Zhou, X.Dong, N.Shen, C.Zhong, and J.Ding (2010).
Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design.
  Nucleic Acids Res, 38, 3399-3413.
PDB codes: 3kt0 3kt3 3kt6 3kt8
20406434 T.M.Bakheet, and A.J.Doig (2010).
Properties and identification of antibiotic drug targets.
  BMC Bioinformatics, 11, 195.  
20176977 W.Paulander, D.I.Andersson, and S.Maisnier-Patin (2010).
Amplification of the gene for isoleucyl-tRNA synthetase facilitates adaptation to the fitness cost of mupirocin resistance in Salmonella enterica.
  Genetics, 185, 305-312.  
19703275 A.Y.Mulkidjanian, and M.Y.Galperin (2009).
On the origin of life in the Zinc world. 2. Validation of the hypothesis on the photosynthesizing zinc sulfide edifices as cradles of life on Earth.
  Biol Direct, 4, 27.  
19902973 J.D.Patrone, J.Yao, N.E.Scott, and G.D.Dotson (2009).
Selective inhibitors of bacterial phosphopantothenoylcysteine synthetase.
  J Am Chem Soc, 131, 16340-16341.  
19656186 M.Konno, T.Sumida, E.Uchikawa, Y.Mori, T.Yanagisawa, S.Sekine, and S.Yokoyama (2009).
Modeling of tRNA-assisted mechanism of Arg activation based on a structure of Arg-tRNA synthetase, tRNA, and an ATP analog (ANP).
  FEBS J, 276, 4763-4779.
PDB codes: 2zue 2zuf
19182784 P.Arora, A.Goyal, V.T.Natarajan, E.Rajakumara, P.Verma, R.Gupta, M.Yousuf, O.A.Trivedi, D.Mohanty, A.Tyagi, R.Sankaranarayanan, and R.S.Gokhale (2009).
Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis.
  Nat Chem Biol, 5, 166-173.
PDB code: 3e53
17461733 U.A.Ochsner, X.Sun, T.Jarvis, I.Critchley, and N.Janjic (2007).
Aminoacyl-tRNA synthetases: essential and still promising targets for new anti-infective agents.
  Expert Opin Investig Drugs, 16, 573-593.  
17501926 W.Paulander, S.Maisnier-Patin, and D.I.Andersson (2007).
Multiple mechanisms to ameliorate the fitness burden of mupirocin resistance in Salmonella typhimurium.
  Mol Microbiol, 64, 1038-1048.  
16505383 A.M.Williams, and S.A.Martinis (2006).
Mutational unmasking of a tRNA-dependent pathway for preventing genetic code ambiguity.
  Proc Natl Acad Sci U S A, 103, 3586-3591.  
16756505 N.G.Richards, and M.S.Kilberg (2006).
Asparagine synthetase chemotherapy.
  Annu Rev Biochem, 75, 629-654.  
16304142 J.G.Hurdle, A.J.O'Neill, and I.Chopra (2005).
Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents.
  Antimicrob Agents Chemother, 49, 4821-4833.  
15504866 J.G.Hurdle, A.J.O'Neill, E.Ingham, C.Fishwick, and I.Chopra (2004).
Analysis of mupirocin resistance and fitness in Staphylococcus aureus by molecular genetic and structural modeling techniques.
  Antimicrob Agents Chemother, 48, 4366-4376.  
15489861 S.Hauenstein, C.M.Zhang, Y.M.Hou, and J.J.Perona (2004).
Shape-selective RNA recognition by cysteinyl-tRNA synthetase.
  Nat Struct Mol Biol, 11, 1134-1141.
PDB code: 1u0b
12709327 J.F.Kokai-Kun, S.M.Walsh, T.Chanturiya, and J.J.Mond (2003).
Lysostaphin cream eradicates Staphylococcus aureus nasal colonization in a cotton rat model.
  Antimicrob Agents Chemother, 47, 1589-1597.  
12163125 A.F.Chalker, and R.D.Lunsford (2002).
Rational identification of new antibacterial drug targets that are essential for viability using a genomics-based approach.
  Pharmacol Ther, 95, 1.  
12762019 O.Nureki, S.Fukai, S.Sekine, A.Shimada, T.Terada, T.Nakama, M.Shirouzu, D.G.Vassylyev, and S.Yokoyama (2001).
Structural basis for amino acid and tRNA recognition by class I aminoacyl-tRNA synthetases.
  Cold Spring Harb Symp Quant Biol, 66, 167-173.  
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 code is shown on the right.