Phosphoribosylaminoimidazolesuccinocarboxamide synthase

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SAICAR synthase
Phosphoribosylaminoimidazole succinocarboxamide synthetase oktamer, Human
EC no.
CAS no.9023-67-0
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
SAICAR synthetase
PDB 1kut EBI.jpg
Structural genomics, protein TM1243, (SAICAR synthetase)
Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary

In molecular biology, the protein domain SAICAR synthase is an enzyme which catalyses a reaction to create SAICAR. In enzymology, this enzyme is also known as phosphoribosylaminoimidazolesuccinocarboxamide synthase (EC It is an enzyme that catalyzes the chemical reaction

ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate

The 3 substrates of this enzyme are ATP, 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate, and L-aspartate, whereas its 3 products are ADP, phosphate, and (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate.

This enzyme belongs to the family of ligases, to be specific those forming carbon-nitrogen bonds as acid-D-amino-acid ligases (peptide synthases). The systematic name of this enzyme class is 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate:L-aspartate ligase (ADP-forming). This enzyme participates in purine metabolism.

This particular protein family is of huge importance as it is found in all three domains of life. It is the seventh step in the pathway of purine biosynthesis. Purines are vital to all cells as they are involved in energy metabolism and DNA synthesis.[1] Furthermore, they are of specific interest to scientific researchers as the study of the purine biosynthesis pathway could lead to the development of chemotherapeutic drugs.[2] This is because most cancers lack a salvage pathway for adenine nucleotides and rely entirely on the SAICAR pathway.[3]

Protein domain[edit]

This protein domain is found in eukaryotes, bacteria and archaea. It is vital for living organisms since it catalyses a step in the purine biosynthesis pathway which aids energy metabolism and DNA synthesis.

Protein domain function[edit]

In bacteria and plants this protein domain only catalyses the synthesis of SAICAR. However, in mammals it also catalyses phosphoribosylaminoimidazole carboxylase (AIRC) activity.[3]

Protein domain structure[edit]

This particular protein is an octamer made up of 8 identical subunits. Each monomer consists of a central domain and a C-terminal alpha helix. The central domain consists of a five-stranded parallel beta sheet flanked by three alpha helices one side of the sheet and two alpha helices on the other, forming a three-layer (alpha beta alpha) sandwich.[4]

Structural studies[edit]

As of late 2007, 10 structures have been solved for this class of enzymes, with PDB accession codes 1A48, 1KUT, 1OBD, 1OBG, 2CNQ, 2CNU, 2CNV, 2GQR, 2GQS, and 2H31.

Other common names[edit]

  • phosphoribosylaminoimidazole-succinocarboxamide synthetase,
  • PurC,
  • SAICAR synthetase,
  • 4-(N-succinocarboxamide)-5-aminoimidazole synthetase,
  • 4-[(N-succinylamino)carbonyl]-5-aminoimidazole ribonucleotide,
  • synthetase,
  • SAICARs,
  • phosphoribosylaminoimidazolesuccinocarboxamide synthetase,
  • 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase.


  1. ^ Brown AM, Hoopes SL, White RH, Sarisky CA (2011). "Purine biosynthesis in archaea: variations on a theme". Biol Direct. 6: 63. doi:10.1186/1745-6150-6-63. PMC 3261824. PMID 22168471.
  2. ^ Cheng X, Lu G, Qi J, Cheng H, Gao F, Wang J, et al. (2010). "Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of SAICAR synthase from Streptococcus suis serotype 2". Acta Crystallogr F. 66 (Pt 8): 909–12. doi:10.1107/S1744309110020518. PMC 2917288. PMID 20693665.
  3. ^ a b Ginder ND, Binkowski DJ, Fromm HJ, Honzatko RB (2006). "Nucleotide complexes of Escherichia coli phosphoribosylaminoimidazole succinocarboxamide synthetase". J Biol Chem. 281 (30): 20680–8. doi:10.1074/jbc.M602109200. PMID 16687397.
  4. ^ Mathews II, Kappock TJ, Stubbe J, Ealick SE (1999). "Crystal structure of Escherichia coli PurE, an unusual mutase in the purine biosynthetic pathway". Structure. 7 (11): 1395–406. doi:10.1016/S0969-2126(00)80029-5. PMID 10574791.