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	PROSITE documentation PDOC00631

All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. Most microorganisms must synthesize folate de novo because they lack the active transport system of higher vertebrate cells which allows these organisms to use dietary folates. Enzymes involved in folate biosynthesis are therefore targets for a variety of antimicrobial agents such as trimethoprim or sulfonamides.

7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (EC 2.7.6.3) (HPPK) catalyzes the attachment of pyrophosphate to 6-hydroxymethyl-7,8-dihydropterin to form 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate. This is the first step in a three-step pathway leading to 7,8-dihydrofolate.

Bacterial HPPK (gene folK or sulD) [1] is a protein of 160 to 270 amino acids. In the lower eukaryote Pneumocystis carinii, HPPK is the central domain of a multifunctional folate synthesis enzyme (gene fas) [2].

As a signature for HPPK, we selected a conserved region located in the central section of these enzymes.

Last update:

July 1999 / Pattern and text revised.

PROSITE method (with tools and information) covered by this documentation:

HPPK, PS00794; 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase signature  (PATTERN)

• Consensus pattern:
  [KRHD]-x-[GA]-[PSAE]-R-x(2)-D-[LIV]-D-[LIVM](2)
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 38
  • detected by PS00794: 33 (true positives)
  • undetected by PS00794: 5 (5 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00794:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00794
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00794
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00794
• View ligand binding statistics of PS00794
• Matching PDB structures: 1CBK 1DY3 1EQ0 1EQM ... [ALL]

1	Authors	Talarico T.L., Ray P.H., Dev I.K., Merrill B.M., Dallas W.S.
	Title	Cloning, sequence analysis, and overexpression of Escherichia coli folK, the gene coding for 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase.
	Source	J. Bacteriol. 174:5971-5977(1992).
	PubMed ID	1325970

2	Authors	Volpes F., Dyer M., Scaife J.G., Darby G., Stammers D.K., Delves C.J.
	Source	Gene 112:213-218(1992).

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