Trifunctional purine synthesis protein

Trifunctional purine synthesis protein
	Representation based on PDB 1rbm
	Existing structural data : 1MEJ , 1MEN , 1MEO , 1NJS , 1RBM , 1RBQ , 1RBY , 1RBZ , 1RC0 , 1RC1 , 1ZLX , 1ZLY , 2QK4 , 2V9Y , 4EW1 , 4EW2 , 4EW3
Properties of human protein
Mass / length primary structure	1009 amino acids
Cofactor	Mn 2+
Isoforms	long, short (433 aa)
Identifier
Gene names	GART AIRS; GARS; GARTF; PAIS; PGFT; PRGS
External IDs	OMIM : 138440 ; UniProt : P22102 ; MGI : 95654 ;
Enzyme Classifications
EC, category	6.3.4.13 , ligase
Response type	Addition of glycine
Substrate	5-phosphoribosylamine + ATP + glycine
Products	Glycine amide ribonucleotide + ADP + P i
EC, category	2.1.2.2 , transferase
Response type	Transfer of a formyl residue
Substrate	Glycine amide ribonucleotide + N 10 -THF
Products	Formylglycine amide ribonucleotide + THF
EC, category	6.3.3.1 , ligase
Response type	Ring closure
Substrate	Formylglycine amidine ribonucleotide + ATP
Products	5-aminoimidazole ribonucleotide + H 2 O + ADP + P i
Occurrence
Parent taxon	Creature
	Orthologue

The trifunctional purine synthesis protein (GARS-AIRS-GART) (also adenosine-3 ) is an enzyme in animals in which three different enzymatic domains are fused to form a protein: phosphoribosylamine glycine ligase (GARS), phosphoribosylglycine amide formyl transferase (GART ) and the phosphoribosylformylglycine amidine cyclo-ligase (AIRS). These activities are part of purine biosynthesis and occur in all living things: as single enzymes in prokaryotes and as partially bifunctional enzymes in yeast .

The domains of adenosine-3 are arranged linearly and catalyze steps 2, 5, and 3 of the ten-step biosynthesis of IMP . The genetic locus in humans for the adenosine 3 gene GART is on chromosome 21 , which is possibly the cause of elevated purine levels in Down syndrome .

Catalyzed reactions

GARS

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

The phosphoribosylamine glycine ligase domain facilitates the addition of glycine to 5-phosphoribosylamine (PRA) to form glycine amide ribonucleotide (GAR).

GART

+ 10-formyl- THF + THF ${\ displaystyle \ longrightarrow}$
${\ displaystyle \ longrightarrow}$

Phosphoribosylglycine amide formyltransferase (GART) catalyzes the formylation of glycine amide ribonucleotide (GAR) to formylglycine amide ribonucleotide (FGAR) using formyl tetrahydrofolate .

AIRS

+ ATP + ADP + P _i + H ₂ O ${\ displaystyle \ longrightarrow}$

The phosphoribosylformylglycine amidine cyclo-ligase domain cyclizes formylglycine amidine ribonucleotide (FGAM) to 5-aminoimidazole ribonucleotide (AIR).

Individual evidence

↑ UniProt P22102
↑ D. Banerjee, K. Nandagopal: Phylogenetic analysis and in silico characterization of the GARS-AIRS-GART gene which codes for a tri-functional enzyme protein involved in de novo purine biosynthesis. In: Molecular biotechnology. Volume 42, Number 3, July 2009, pp. 306-319, doi : 10.1007 / s12033-009-9160-1 . PMID 19301155 .
↑ D. Patterson, S. Graw, C. Jones: Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21. In: Proceedings of the National Academy of Sciences . Volume 78, Number 1, January 1981, pp. 405-409, PMID 6941256 . PMC 319062 (free full text).

Web links

Wikibooks: Purine Metabolism - Learning and Teaching Materials

[1] UniProt P22102

[2] D. Banerjee, K. Nandagopal: Phylogenetic analysis and in silico characterization of the GARS-AIRS-GART gene which codes for a tri-functional enzyme protein involved in de novo purine biosynthesis. In: Molecular biotechnology. Volume 42, Number 3, July 2009, pp. 306-319, doi : 10.1007 / s12033-009-9160-1 . PMID 19301155 .

[3] D. Patterson, S. Graw, C. Jones: Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21. In: Proceedings of the National Academy of Sciences . Volume 78, Number 1, January 1981, pp. 405-409, PMID 6941256 . PMC 319062 (free full text).