Multifunctional protein ADE2

Multifunctional protein ADE2
Phosphoribosylaminoimidazole carboxylase / phosphoribosylaminoimidazole succinocarboxamide synthetase octamer, human according to PDB  2H31
Existing structural data : 2H31 ,
Properties of human protein
Mass / length primary structure	424 amino acids
Secondary to quaternary structure	Homooctamer
Isoforms	2
Identifier
Gene name	PAICS
External IDs	OMIM :  172439 UniProt :  P22234
Enzyme Classifications
EC, category	4.1.1.21 ,  lyase
Response type	Addition of carboxylate
Substrate	AIR + H 2 O
Products	CAIR
EC, category	6.3.2.6 ,  ligase
Response type	Addition of aspartate
Substrate	CAIR + ATP + aspartate
Products	SAICAR + ADP + P i
Occurrence
Parent taxon	Creature
Orthologue
	human	House mouse
Entrez	10606	67054
Ensemble	ENSG00000128050	ENSMUSG00000029247
UniProt	P22234	Q9DCL9
Refseq (mRNA)	NM_001079525	NM_025939
Refseq (protein)	NP_001072993	NP_080215
Gene locus	Chr 4: 56.44 - 56.46 Mb	Chr 5: 76.95 - 76.97 Mb
PubMed search	10606	67054

The multifunctional protein ADE2 ( gene name: PAICS ) is an enzyme in vertebrates in which two different enzymatic domains are fused into a protein: phosphoribosylaminoimidazole carboxylase (AIRC) and phosphoribosylaminoimidazole succinocarboxamide synthase (SAICAR synthase). These activities are part of purine biosynthesis and occur in all living things: as individual enzymes in prokaryotes and as fusion proteins in vertebrates, fungi and plants.

The domains of ADE2 catalyze steps 6 and 7 of the ten-step biosynthesis of IMP . The SAICAR synthase is inhibited by IMP or maleate . The human ADE2 complexes to form an octamer .

Catalyzed reactions

AIRC

+ CO ₂   ${\displaystyle \longrightarrow }$
${\displaystyle \longrightarrow }$ 

5-Aminoimidazole ribonucleotide (AIR) is carboxylated to 5-aminoimidazole-4-carboxylatribonucleotide (CAIR).

SAICAR synthase

+ + ATP   + ADP + P _i ${\displaystyle \longrightarrow }$
${\displaystyle \longrightarrow }$ 

CAIR and aspartic acid are ligated, with consumption of ATP.

Individual evidence

1. ↑ UniProt P22234
2. ↑ PROSITE : PROSITE documentation PDOC0080 (English)
3. ↑ Phosphoribosylaminoimidazole carboxylase, ATPase subunit (IPR005875) <InterPro <EMBL-EBI. Retrieved March 3, 2019 . 
4. ↑ SW Nelson, DJ Binkowski et al. a .: Mechanism of action of Escherichia coli phosphoribosylaminoimidazolesuccinocarboxamide synthetase. In: Biochemistry . Volume 44, Number 2, January 2005, pp. 766-774, doi : 10.1021 / bi048191w . PMID 15641804 .
5. ↑ SX Li, YP Tong et al. a .: Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis. In: Journal of molecular biology . Volume 366, number 5, March 2007, pp. 1603-1614, doi : 10.1016 / j.jmb.2006.12.027 . PMID 17224163 .

Web links

Wikibooks: Purine Metabolism  - Learning and Teaching Materials