Summary: SAICAR synthetase
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Phosphoribosylaminoimidazolesuccinocarboxamide synthase Edit Wikipedia article
Phosphoribosylaminoimidazole succinocarboxamide synthetase oktamer, Human
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
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 22.214.171.124). 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. 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. This is because most cancers lack a salvage pathway for adenine nucleotides and rely entirely on the SAICAR pathway.
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.
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.
Other common names
- phosphoribosylaminoimidazole-succinocarboxamide synthetase,
- SAICAR synthetase,
- 4-(N-succinocarboxamide)-5-aminoimidazole synthetase,
- 4-[(N-succinylamino)carbonyl]-5-aminoimidazole ribonucleotide,
- phosphoribosylaminoimidazolesuccinocarboxamide synthetase,
- 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase.
- Brown AM, Hoopes SL, White RH, Sarisky CA (2011). "Purine biosynthesis in archaea: variations on a theme.". Biol Direct. 6: 63. PMC . PMID 22168471. doi:10.1186/1745-6150-6-63.
- 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. PMC . PMID 20693665. doi:10.1107/S1744309110020518.
- Ginder ND, Binkowski DJ, Fromm HJ, Honzatko RB (2006). "Nucleotide complexes of Escherichia coli phosphoribosylaminoimidazole succinocarboxamide synthetase.". J Biol Chem. 281 (30): 20680–8. PMID 16687397. doi:10.1074/jbc.M602109200.
- 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. PMID 10574791. doi:10.1016/S0969-2126(00)80029-5.
- LUKENS LN, BUCHANAN JM (1959). "Biosynthesis of the purines. XXIV. The enzymatic synthesis of 5-amino-1-ribosyl-4-imidazolecarboxylic acid 5'-phosphate from 5-amino-1-ribosylimidazole 5'-phosphate and carbon dioxide". J. Biol. Chem. 234 (7): 1799–805. PMID 13672967.
- Parker J (1984). "Identification of the purC gene product of Escherichia coli". J. Bacteriol. 157 (3): 712–7. PMC . PMID 6365889.
- Ebbole DJ, Zalkin H (1987). "Cloning and characterization of a 12-gene cluster from Bacillus subtilis encoding nine enzymes for de novo purine nucleotide synthesis". J. Biol. Chem. 262 (17): 8274–87. PMID 3036807.
- Chen ZD, Dixon JE, Zalkin H (1990). "Cloning of a chicken liver cDNA encoding 5-aminoimidazole ribonucleotide carboxylase and 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase by functional complementation of Escherichia coli pur mutants". Proc. Natl. Acad. Sci. U.S.A. 87 (8): 3097–101. PMC . PMID 1691501. doi:10.1073/pnas.87.8.3097.
- O'Donnell AF, Tiong S, Nash D, Clark DV (2000). "The Drosophila melanogaster ade5 gene encodes a bifunctional enzyme for two steps in the de novo purine synthesis pathway". Genetics. 154 (3): 1239–53. PMC . PMID 10757766.
- Nelson SW, Binkowski DJ, Honzatko RB, Fromm HJ (2005). "Mechanism of action of Escherichia coli phosphoribosylaminoimidazolesuccinocarboxamide synthetase". Biochemistry. 44 (2): 766–74. PMID 15641804. doi:10.1021/bi048191w.
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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.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
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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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|Seed source:||Pfam-B_1426 (release 3.0)|
|Author:||Finn RD, Bateman A|
|Number in seed:||680|
|Number in full:||4839|
|Average length of the domain:||238.40 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||82.79 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||17|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
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Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
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There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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There are 2 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 seqence.
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