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PDBsum entry 12as

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protein ligands Protein-protein interface(s) links
Ligase PDB id
12as
Jmol
Contents
Protein chains
327 a.a. *
Ligands
ASN ×2
AMP ×2
Waters ×203
* Residue conservation analysis
PDB id:
12as
Name: Ligase
Title: Asparagine synthetase mutant c51a, c315a complexed with l- asparagine and amp
Structure: Asparagine synthetase. Chain: a, b. Synonym: l-aspartate\:ammonia ligase (amp-forming). Engineered: yes. Mutation: yes
Source: Escherichia coli k12. Organism_taxid: 83333. Strain: k-12. Gene: asna. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.20Å     R-factor:   0.164     R-free:   0.287
Authors: T.Nakatsu,H.Kato,J.Oda
Key ref: T.Nakatsu et al. (1998). Crystal structure of asparagine synthetase reveals a close evolutionary relationship to class II aminoacyl-tRNA synthetase. Nat Struct Biol, 5, 15-19. PubMed id: 9437423
Date:
02-Dec-97     Release date:   30-Dec-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00963  (ASNA_ECOLI) -  Aspartate--ammonia ligase
Seq:
Struc:
330 a.a.
327 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.6.3.1.1  - Aspartate--ammonia ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-aspartate + NH3 = AMP + diphosphate + L-asparagine
ATP
+ L-aspartate
+ NH(3)
=
AMP
Bound ligand (Het Group name = AMP)
corresponds exactly
+ diphosphate
+
L-asparagine
Bound ligand (Het Group name = ASN)
corresponds exactly
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     L-asparagine biosynthetic process   5 terms 
  Biochemical function     nucleotide binding     5 terms  

 

 
    reference    
 
 
Nat Struct Biol 5:15-19 (1998)
PubMed id: 9437423  
 
 
Crystal structure of asparagine synthetase reveals a close evolutionary relationship to class II aminoacyl-tRNA synthetase.
T.Nakatsu, H.Kato, J.Oda.
 
  ABSTRACT  
 
The crystal structure of E. coli asparagine synthetase has been determined by X-ray diffraction analysis at 2.5 A resolution. The overall structure of the enzyme is remarkably similar to that of the catalytic domain of yeast aspartyl-tRNA synthetase despite low sequence similarity. These enzymes have a common reaction mechanism that implies the formation of an aminoacyl-adenylate intermediate. The active site architecture and most of the catalytic residues are also conserved in both enzymes. These proteins have probably evolved from a common ancestor even though their sequence similarities are small. The functional and structural similarities of both enzymes suggest that new enzymatic activities would generally follow the recruitment of a protein catalyzing a similar chemical reaction.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20384986 C.C.Reddy, S.S.Rani, B.Offmann, and R.Sowdhamini (2010).
Systematic search for putative new domain families in Mycoplasma gallisepticum genome.
  BMC Res Notes, 3, 98.  
18346928 I.Tobar, F.D.González-Nilo, A.M.Jabalquinto, and E.Cardemil (2008).
Relevance of Arg457 for the nucleotide affinity of Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase.
  Int J Biochem Cell Biol, 40, 1883-1889.  
17690095 D.Thompson, C.Lazennec, P.Plateau, and T.Simonson (2007).
Ammonium scanning in an enzyme active site. The chiral specificity of aspartyl-tRNA synthetase.
  J Biol Chem, 282, 30856-30868.  
17329242 K.Sheppard, P.M.Akochy, J.C.Salazar, and D.Söll (2007).
The Helicobacter pylori amidotransferase GatCAB is equally efficient in glutamine-dependent transamidation of Asp-tRNAAsn and Glu-tRNAGln.
  J Biol Chem, 282, 11866-11873.  
17185229 J.A.Gutierrez, Y.X.Pan, L.Koroniak, J.Hiratake, M.S.Kilberg, and N.G.Richards (2006).
An inhibitor of human asparagine synthetase suppresses proliferation of an L-asparaginase-resistant leukemia cell line.
  Chem Biol, 13, 1339-1347.  
16387658 J.D.Mougous, D.H.Lee, S.C.Hubbard, M.W.Schelle, D.J.Vocadlo, J.M.Berger, and C.R.Bertozzi (2006).
Molecular basis for G protein control of the prokaryotic ATP sulfurylase.
  Mol Cell, 21, 109-122.
PDB code: 1zun
16756505 N.G.Richards, and M.S.Kilberg (2006).
Asparagine synthetase chemotherapy.
  Annu Rev Biochem, 75, 629-654.  
16051603 K.S.Champagne, M.Sissler, Y.Larrabee, S.Doublié, and C.S.Francklyn (2005).
Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog.
  J Biol Chem, 280, 34096-34104.
PDB codes: 1z7m 1z7n
15660995 M.C.Vega, P.Zou, F.J.Fernandez, G.E.Murphy, R.Sterner, A.Popov, and M.Wilmanns (2005).
Regulation of the hetero-octameric ATP phosphoribosyl transferase complex from Thermotoga maritima by a tRNA synthetase-like subunit.
  Mol Microbiol, 55, 675-686.
PDB code: 1usy
15562516 N.Rekha, S.M.Machado, C.Narayanan, A.Krupa, and N.Srinivasan (2005).
Interaction interfaces of protein domains are not topologically equivalent across families within superfamilies: Implications for metabolic and signaling pathways.
  Proteins, 58, 339-353.  
15522455 R.Geslain, and L.Ribas de Pouplana (2004).
Regulation of RNA function by aminoacylation and editing?
  Trends Genet, 20, 604-610.  
12913115 C.Francklyn (2003).
tRNA synthetase paralogs: evolutionary links in the transition from tRNA-dependent amino acid biosynthesis to de novo biosynthesis.
  Proc Natl Acad Sci U S A, 100, 9650-9652.  
12874385 H.Roy, H.D.Becker, J.Reinbolt, and D.Kern (2003).
When contemporary aminoacyl-tRNA synthetases invent their cognate amino acid metabolism.
  Proc Natl Acad Sci U S A, 100, 9837-9842.  
12684518 M.Goto, R.Omi, I.Miyahara, M.Sugahara, and K.Hirotsu (2003).
Structures of argininosuccinate synthetase in enzyme-ATP substrates and enzyme-AMP product forms: stereochemistry of the catalytic reaction.
  J Biol Chem, 278, 22964-22971.
PDB codes: 1j1z 1j20 1j21 1kh3
14665676 P.O'Donoghue, and Z.Luthey-Schulten (2003).
On the evolution of structure in aminoacyl-tRNA synthetases.
  Microbiol Mol Biol Rev, 67, 550-573.  
14654681 W.A.Loenen (2003).
Tracking EcoKI and DNA fifty years on: a golden story full of surprises.
  Nucleic Acids Res, 31, 7059-7069.  
11880622 B.Min, J.T.Pelaschier, D.E.Graham, D.Tumbula-Hansen, and D.Söll (2002).
Transfer RNA-dependent amino acid biosynthesis: an essential route to asparagine formation.
  Proc Natl Acad Sci U S A, 99, 2678-2683.  
12458790 C.Francklyn, J.J.Perona, J.Puetz, and Y.M.Hou (2002).
Aminoacyl-tRNA synthetases: versatile players in the changing theater of translation.
  RNA, 8, 1363-1372.  
11557806 D.T.Dryden, N.E.Murray, and D.N.Rao (2001).
Nucleoside triphosphate-dependent restriction enzymes.
  Nucleic Acids Res, 29, 3728-3741.  
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.  
  11106165 P.A.Reche (2000).
Lipoylating and biotinylating enzymes contain a homologous catalytic module.
  Protein Sci, 9, 1922-1929.  
10782085 P.Schimmel, and L.Ribas De Pouplana (2000).
Footprints of aminoacyl-tRNA synthetases are everywhere.
  Trends Biochem Sci, 25, 207-209.  
10679458 S.Blanquet, Y.Mechulam, and E.Schmitt (2000).
The many routes of bacterial transfer RNAs after aminoacylation.
  Curr Opin Struct Biol, 10, 95.  
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.  
9789001 A.W.Curnow, D.L.Tumbula, J.T.Pelaschier, B.Min, and D.Söll (1998).
Glutamyl-tRNA(Gln) amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis.
  Proc Natl Acad Sci U S A, 95, 12838-12843.  
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.  
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
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.