6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase

Function

6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) or 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase is a prokaryotic enzyme which is part of the folate synthesis pathway. HPPK catalyzes the attachment of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HMDP) to form 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate. Mg+2 ion is important for binding ATP and HMDP.^[1]

The Plasmodium parasites encode a protein fused of HPPK and dihydroperoate synthase (HPPK-DHPS) which catalyse reaction in the folate biosynthesis pathway^[2].

The reaction catalyzed by HPPK involves the transfer of a pyrophosphate group from ATP to HMDP, leading to the formation of HMDPTP and ADP. This phosphorylation step is essential for subsequent reactions in the folate biosynthesis pathway, leading to the production of THF.

Relevance

HPPK is a potential target for antimicrobial drugs like trimethoprim and sulfonamides.

Structural highlights

Three loop regions surround the HPPK active site. Upon binding of ATP, the region (purple) changes its conformation and enables the binding of HMDP. . Water molecules are shown as red spheres.

3D structures of HPPK

HPPK 3D structures