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53  structures 7475  species 2  interactions 8429  sequences 43  architectures

Family: SAICAR_synt (PF01259)

Summary: SAICAR synthetase

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This is the Wikipedia entry entitled "Phosphoribosylaminoimidazolesuccinocarboxamide synthase". More...

Phosphoribosylaminoimidazolesuccinocarboxamide synthase Edit Wikipedia article

SAICAR synthase
Phosphoribosylaminoimidazole succinocarboxamide synthetase oktamer, Human
EC number6.3.2.6
CAS number9023-67-0
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)

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

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

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

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

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

  • 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.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

SAICAR synthetase Provide feedback

Also known as Phosphoribosylaminoimidazole-succinocarboxamide synthase.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR028923

Phosphoribosylaminoimidazole-succinocarboxamide synthase (EC) (SAICAR synthetase) catalyses the seventh step in the de novo purine biosynthetic pathway; the ATP-dependent conversion of 5'-phosphoribosyl-5-aminoimidazole-4-carboxylic acid and aspartic acid to SAICAR [PUBMED:1574589].

This domain can be found in SAICAR synthetases as a monofunctional protein from the bacteria (purC), fungi (ADE1) and plants (Pur7). In animals, this domain can be found in the N-terminal domain of a multifunctional enzyme (ADE2) possessing both the SAICAR synthetase and the phosphoribosylaminoimidazole carboxylase (AIR carboxylase) activity.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_1426 (release 3.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD , Bateman A
Number in seed: 617
Number in full: 8429
Average length of the domain: 240.30 aa
Average identity of full alignment: 33 %
Average coverage of the sequence by the domain: 81.25 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.7 19.7
Trusted cut-off 19.8 19.7
Noise cut-off 18.8 19.6
Model length: 254
Family (HMM) version: 19
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Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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There are 2 interactions for this family. More...



For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the SAICAR_synt domain has been found. There are 53 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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