PDBsum entry 1kp2

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protein ligands links
Ligase PDB id
Protein chain
431 a.a. *
PO4 ×3
Waters ×286
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structure of e. Coli argininosuccinate synthetase in with atp
Structure: Argininosuccinate synthetase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: argg. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
2.00Å     R-factor:   0.177     R-free:   0.216
Authors: C.T.Lemke,P.L.Howell
Key ref:
C.T.Lemke and P.L.Howell (2002). Substrate induced conformational changes in argininosuccinate synthetase. J Biol Chem, 277, 13074-13081. PubMed id: 11809762 DOI: 10.1074/jbc.M112436200
27-Dec-01     Release date:   17-Apr-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P0A6E4  (ASSY_ECOLI) -  Argininosuccinate synthase
447 a.a.
431 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Argininosuccinate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Urea Cycle and Arginine Biosynthesis
      Reaction: ATP + L-citrulline + L-aspartate = AMP + diphosphate + N(omega)- (L-arginino)succinate
Bound ligand (Het Group name = ATP)
corresponds exactly
+ L-citrulline
+ L-aspartate
Bound ligand (Het Group name = PO4)
matches with 55.56% similarity
+ N(omega)- (L-arginino)succinate
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     cellular amino acid biosynthetic process   2 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1074/jbc.M112436200 J Biol Chem 277:13074-13081 (2002)
PubMed id: 11809762  
Substrate induced conformational changes in argininosuccinate synthetase.
C.T.Lemke, P.L.Howell.
Argininosuccinate synthetase (AS) is the rate-limiting enzyme of both the urea and arginine-citrulline cycles. In mammals, deficiency of AS leads to citrullinemia, a debilitating and often fatal autosomal recessive urea cycle disorder, whereas its overexpression for sustained nitric oxide production via the arginine-citrulline cycle leads to the potentially fatal hypotension associated with septic and cytokine-induced circulatory shock. The crystal structures of Escherichia coli argininosuccinate synthetase (EAS) in complex with ATP and with ATP and citrulline have been determined at 2.0-A resolution. These are the first EAS structures to be solved in the presence of a nucleotide substrate and clearly identify the residues that interact with both ATP and citrulline. Two distinct conformations are revealed for ATP, both of which are believed to be catalytically relevant. In addition, comparisons of these EAS structures with those of the apoenzyme and EAS complexed with aspartate and citrulline (Lemke, C. T., and Howell, P. L. (2001) Structure (Lond.) 9, 1153-1164) provide structural evidence of ATP-induced conformational changes in the nucleotide binding domain. Combined, these structures also provide structural explanations of some of the observed kinetic properties of the enzyme and have enabled a detailed enzymatic mechanism of AS catalysis to be proposed.
  Selected figure(s)  
Figure 1.
Fig. 1. The argininosuccinate synthetase mechanism. Step 1, activated citrulline-adenylate is formed, releasing inorganic pyrophosphate. Step 2, nucleophilic attack by aspartate amino group forms argininosuccinate and releases AMP.
Figure 8.
Fig. 8. ATP conformations. The conformations of ATP observed in lysyl tRNA synthetase (a), EAS ( b), and NAD^+ synthetase (c) are shown. The dashed lines are drawn between the -phosphate of ATP and nucleophile.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 13074-13081) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19491403 J.R.Guerreiro, C.Lameu, E.F.Oliveira, C.F.Klitzke, R.L.Melo, E.Linares, O.Augusto, J.W.Fox, I.Lebrun, S.M.Serrano, and A.C.Camargo (2009).
Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production.
  J Biol Chem, 284, 20022-20033.  
18323623 T.Karlberg, R.Collins, S.van den Berg, A.Flores, M.Hammarström, M.Högbom, L.Holmberg Schiavone, and J.Uppenberg (2008).
Structure of human argininosuccinate synthetase.
  Acta Crystallogr D Biol Crystallogr, 64, 279-286.
PDB code: 2nz2
18073113 M.Kuratani, Y.Yoshikawa, Y.Bessho, K.Higashijima, T.Ishii, R.Shibata, S.Takahashi, K.Yutani, and S.Yokoyama (2007).
Structural basis of the initial binding of tRNA(Ile) lysidine synthetase TilS with ATP and L-lysine.
  Structure, 15, 1642-1653.
PDB codes: 2e21 2e89
16082501 E.Curis, I.Nicolis, C.Moinard, S.Osowska, N.Zerrouk, S.Bénazeth, and L.Cynober (2005).
Almost all about citrulline in mammals.
  Amino Acids, 29, 177-205.  
16039592 Y.Ikeuchi, A.Soma, T.Ote, J.Kato, Y.Sekine, and T.Suzuki (2005).
molecular mechanism of lysidine synthesis that determines tRNA identity and codon recognition.
  Mol Cell, 19, 235-246.  
12709047 A.Husson, C.Brasse-Lagnel, A.Fairand, S.Renouf, and A.Lavoinne (2003).
Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle.
  Eur J Biochem, 270, 1887-1899.  
12815590 H.Z.Gao, K.Kobayashi, A.Tabata, H.Tsuge, M.Iijima, T.Yasuda, H.S.Kalkanoglu, A.Dursun, A.Tokatli, T.Coskun, F.K.Trefz, D.Skladal, H.Mandel, J.Seidel, S.Kodama, S.Shirane, T.Ichida, S.Makino, M.Yoshino, J.H.Kang, M.Mizuguchi, B.A.Barshop, S.Fuchinoue, S.Seneca, S.Zeesman, I.Knerr, M.Rodés, P.Wasant, I.Yoshida, L.De Meirleir, M.Abdul Jalil, L.Begum, M.Horiuchi, N.Katunuma, S.Nakagawa, and T.Saheki (2003).
Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients.
  Hum Mutat, 22, 24-34.  
12454470 C.T.Lemke, G.D.Smith, and P.L.Howell (2002).
S-SAD, Se-SAD and S/Se-SIRAS using Cu Kalpha radiation: why wait for synchrotron time?
  Acta Crystallogr D Biol Crystallogr, 58, 2096-2101.  
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.