PPAT
Description
The PPAT (phosphoribosyl pyrophosphate amidotransferase) is a protein-coding gene located on chromosome 4.
Amidophosphoribosyltransferase (ATase), also known as glutamine phosphoribosylpyrophosphate amidotransferase (GPAT), is an enzyme responsible for catalyzing the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) into 5-phosphoribosyl-1-amine (PRA), using the amine group from a glutamine side-chain. This is the committing step in de novo purine synthesis. In humans it is encoded by the PPAT (phosphoribosyl pyrophosphate amidotransferase) gene. ATase is a member of the purine/pyrimidine phosphoribosyltransferase family.
== Structure and function ==
The enzyme consists of two domains: a glutaminase domain that produces ammonia from glutamine by hydrolysis and a phosphoribosyltransferase domain that binds the ammonia to ribose-5-phosphate. Coordination between the two active sites of enzyme give it special complexity. The glutaminase domain is homologous to other N-terminal nucleophile (Ntn) hydrolases such as carbamoyl phosphate synthetase (CPSase). Nine invariant residues among the sequences of all Ntn amidotransferases play key catalytic, substrate binding or structural roles. A terminal cysteine residue acts as the nucleophile in the first part of the reaction, analogous to the cysteine of a catalytic triad. The free N terminus acts as a base to activate the nucleophile and protonate the leaving group in the hydrolytic reaction, in this case ammonia.
PPAT is also known as ATASE, GPAT, PRAT.
Associated Diseases
- adult acute lymphoblastic leukemia
- systemic lupus erythematosus
- polyarteritis nodosa
- lymphoblastic lymphoma
