Disease relevance of C01300

• Equilibrium and kinetic studies of substrate binding to 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Escherichia coli [1].
• The structure and function of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Haemophilus influenzae [2].
• Crystal structure of the bifunctional dihydroneopterin aldolase/6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Streptococcus pneumoniae [3].

High impact information on C01300

• The structure of the binary complex with the product 6-hydroxymethyl-7,8-dihydropterin has defined the location of the active site [4].
• The three-dimensional structure of the bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/dihydropteroate synthase of Saccharomyces cerevisiae [5].
• Dihydroneopterin aldolase (DHNA) catalyses a retroaldol reaction yielding 6-hydroxymethyl-7,8-dihydropterin, a biosynthetic precursor of the vitamin, tetrahydrofolate [6].
• The first domain (HPPK) catalyses the pyrophosphorylation of 6-hydroxymethyl-7,8-dihydropterin (dihydropterin) by ATP, leading to 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (dihydropterinPP(i)) and AMP [7].
• A protein encoded by sulD, one of four genes in a previously cloned folate biosynthetic operon of Streptococcus pneumoniae, had been shown to harbor 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase activity [8].

Biological context of C01300

• It forms part of a longer coding sequence, located on chromosome 8, that also specifies 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (CH2OH-H2pterinPP kinase) at its 5' proximal end [9].
• Two were identified as pseudogenes (PsifolP and PsifolK) homologous to folP and folK genes, which encode dihydropteroate synthase (DHPS) and 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), respectively, in other bacteria [10].

Associations of C01300 with other chemical compounds

• The plant enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase (HPPK/DHPS) is a mitochondrial bifunctional protein involved in tetrahydrofolate synthesis [7].
• 1. The Km value for 6-hydroxymethyl-7,8-dihydropterin was 3.6 microM in 50 mM Tris buffer, pH 8 [11].

Gene context of C01300

• The last gene, sulD, encodes a 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase [12].

Analytical, diagnostic and therapeutic context of C01300

• Unusual conformational changes in 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as revealed by X-ray crystallography and NMR [13].
• The roles of a pair of conserved positively charged residues R82 and R92 at a catalytic loop of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) have been investigated by site-directed mutagenesis and biochemical analysis [14].

References