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

2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase
Ec Number:	2.7.6.3
Cas Number:	37278-23-2
Go Code:	0003848
Width:	270

Symbol:	HPPK
7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK)
Pfam:	PF01288
Interpro:	IPR000550
Prosite:	PDOC00631
Scop:	1hka
Cdd:	cd00483

In enzymology, a 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase is an enzyme that catalyzes the chemical reaction

ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine

\rightleftharpoons AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate

Thus, the two substrates of this enzyme are ATP and 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine, whereas its two products are AMP and (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate.

This enzyme belongs to the family of transferases, specifically those transferring two phosphorus-containing groups (diphosphotransferases). The systematic name of this enzyme class is ATP:2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine 6'-diphosphotransferase. Other names in common use include 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase, H2-pteridine-CH2OH pyrophosphokinase, 7,8-dihydroxymethylpterin-pyrophosphokinase, HPPK, 7,8-dihydro-6-hydroxymethylpterin pyrophosphokinase, and hydroxymethyldihydropteridine pyrophosphokinase. This enzyme participates in folate biosynthesis.

This enzyme catalyses the first step in a three-step pathway leading to 7,8 dihydrofolate. Bacterial HPPK (gene folK or sulD) is a protein of 160 to 270 amino acids.^[1] In the lower eukaryote Pneumocystis carinii, HPPK is the central domain of a multifunctional folate synthesis enzyme (gene fas).^[2]

Structural studies

As of late 2007, 23 structures have been solved for this class of enzymes, with PDB accession codes,,,,,,,,,,,,,,,,,,,,,, and .

Further reading

• Richey DP, Brown GM . 1969 . The biosynthesis of folic acid. IX. Purification and properties of the enzymes required for the formation of dihydropteroic acid . J. Biol. Chem. . 244 . 1582 - 92 . 4304228 . 6 . 10.1016/S0021-9258(18)91799-0 . free .
• Book: Richey DP, Brown GM . Hydroxymethyldihydropteridine pyrophosphokinase and dihydropteroate synthetase from Escherichia coli . 1971 . Vitamins and Coenzymes . Methods Enzymol. . 18B . 765 - 771 . 10.1016/s0076-6879(71)18150-5. 978-0-12-181880-7 .
• Shiota T, Baugh CM, Jackson R, Dillard R . 1969 . The enzymatic synthesis of hydroxymethyldihydropteridine pyrophosphate and dihydrofolate . Biochemistry . 8 . 5022 - 8 . 4312465 . 10.1021/bi00840a052 . 12 .

Notes and References

1. Talarico TL, Ray PH, Dev IK, Merrill BM, Dallas WS . Cloning, sequence analysis, and overexpression of Escherichia coli folK, the gene coding for 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase . J. Bacteriol. . 174 . 18 . 5971–7 . September 1992 . 1325970 . 207135 . 10.1128/jb.174.18.5971-5977.1992.
2. Volpe F, Dyer M, Scaife JG, Darby G, Stammers DK, Delves CJ . The multifunctional folic acid synthesis fas gene of Pneumocystis carinii appears to encode dihydropteroate synthase and hydroxymethyldihydropterin pyrophosphokinase . Gene . 112 . 2 . 213–8 . March 1992 . 1313386 . 10.1016/0378-1119(92)90378-3.