phosphoribosylformylglycinamidine cyclo-ligase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + ATP = 5-amino-1-(5-phospho-D-ribosyl)imidazole + ADP + 2 H+ + phosphate. [EC:6.3.3.1, RHEA:23032]

Phosphoribosylformylglycinamidine cyclo-ligase (FGAM cyclo-ligase) catalyzes the formation of a cyclic molecule, 5,10-methenyltetrahydrofolate, from the linear molecule N-formylglycinamidine ribonucleotide (FGAM) and tetrahydrofolate (THF). This reaction is a key step in the purine biosynthesis pathway. FGAM cyclo-ligase is a bifunctional enzyme, possessing both synthase and cyclo-ligase activities. It utilizes the energy from the hydrolysis of ATP to form the carbon-nitrogen bond between the formyl group of FGAM and the N-5 position of THF. This process involves the following steps: 1. The enzyme binds both FGAM and THF. 2. FGAM is positioned in the active site, adjacent to the N-5 position of THF. 3. The enzyme promotes the formation of a Schiff base intermediate between the formyl group of FGAM and the N-5 position of THF. 4. This intermediate undergoes a conformational change, bringing the formyl group closer to the N-5 position of THF. 5. The carbon-nitrogen bond is formed, resulting in the release of a water molecule and the formation of 5,10-methenyltetrahydrofolate. The overall reaction is exergonic, driving the purine biosynthesis pathway forward. FGAM cyclo-ligase is an essential enzyme for the synthesis of purine nucleotides, which are vital for DNA and RNA synthesis, as well as for numerous other cellular processes. Mutations in the gene encoding FGAM cyclo-ligase can lead to severe metabolic disorders, emphasizing the critical role of this enzyme in human health.'
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Proteins (2)

Compounds (4)