2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + ATP = (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate + AMP + 2 H+. [EC:2.7.6.3, RHEA:11412]

2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase (DHPS) catalyzes the phosphorylation of 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine (dihydropteroate) to form dihydrofolate. This reaction is the first committed step in the biosynthesis of tetrahydrofolate (THF), a crucial coenzyme for a variety of metabolic pathways, including purine and pyrimidine synthesis, amino acid metabolism, and the synthesis of deoxythymidine monophosphate (dTMP) for DNA replication. DHPS utilizes ATP as the phosphate donor and transfers the γ-phosphate group to the dihydropteroate substrate. The reaction mechanism involves a two-step process: first, DHPS forms a phosphorylated intermediate with ATP, and then the phosphate group is transferred to the dihydropteroate. The enzyme exhibits a high degree of specificity for its substrates and is essential for the synthesis of THF, which is required for cell growth and proliferation. Mutations in the DHPS gene can lead to defects in folate metabolism and can be associated with various human diseases, including megaloblastic anemia and neurodevelopmental disorders. The enzyme is a key target for antibacterial and antifungal drugs that inhibit folate synthesis and block the growth of pathogenic organisms.'
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Proteins (1)

Compounds (5)