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PRPS1

Ribose-phosphate diphosphokinase
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Phosphoribosyl pyrophosphate synthase 1, hexamer, Human
Identifiers
EC number 2.7.6.1
CAS number 9031-46-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
phosphoribosyl pyrophosphate synthetase 1
Identifiers
Symbol PRPS1
Entrez 5631
HUGO 9462
OMIM 311850
RefSeq NM_002764
UniProt P60891
Other data
EC number 2.7.6.1
Locus Chr. X q21-q27
phosphoribosyl pyrophosphate synthetase 2
Identifiers
Symbol PRPS2
Entrez 5634
HUGO 9465
OMIM 311860
RefSeq NM_002765
UniProt P11908
Other data
EC number 2.7.6.1
Locus Chr. X pter-q21

Ribose-phosphate diphosphokinase (or phosphoribosyl pyrophosphate synthetase or ribose-phosphate pyrophosphokinase) is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under EC 2.7.6.1.

The enzyme is involved in the synthesis of nucleotides (purines and pyrimidines), cofactors NAD and NADP, and amino acids histidine and tryptophan, linking these biosynthetic processes to the pentose phosphate pathway, from which the substrate ribose 5-phosphate is derived. Ribose 5-phosphate is produced by the HMP Shunt Pathway from Glucose-6-Phosphate. The product phosphoribosyl pyrophosphate acts as an essential component of the purine salvage pathway and the de novo synthesis of purines. Dysfunction of the enzyme would thereby undermine purine metabolism. Ribose-phosphate pyrophosphokinase exists in bacteria, plants, and animals, and there are three isoforms of human ribose-phosphate pyrophosphokinase. In humans, the genes encoding the enzyme are located on the X chromosome.

Ribose-phosphate diphosphokinase transfers the diphosphoryl group from Mg-ATP (Mg2+ coordinated to ATP) to ribose 5-phosphate. The enzymatic reaction begins with the binding of ribose 5-phosphate, followed by binding of Mg-ATP to the enzyme. In the transition state upon binding of both substrates, the diphosphate is transferred. The enzyme first releases AMP before releasing the product phosphoribosyl pyrophosphate. Experiments using oxygen 18 labelled water demonstrate that the reaction mechanism proceeds with the nucleophilic attack of the anomeric hydroxyl group of ribose 5-phosphate on the beta-phosphorus of ATP in an SN2 reaction.


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Wikipedia

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