TTD Target ID: TTDS00237

Target Information
Name	Dihydropteroate synthetase
Type of target	Successful target
Synonyms	DHPS
	Dihydropteroate pyrophosphorylase
	Dihydropteroate synthase
	H2Pte synthase
Disease	Bacterial infections    [1]
	Malaria    [2][3][4]
Drug(s)	Dapsone		Approved	Pneumocystis carinii pneumonia	[5]
	Sulfacytine		Approved	Urinary tract infections	[6]
	Sulfadiazine		Approved	Urinary tract infections	[7]
	Sulfadoxine		Approved	Malaria	[8]
	Sulfamerazine		Approved	Bacterial infections	[9]
	Sulfamethazine		Approved	Bacterial infections	[10]
	Sulfamethizole		Approved	Urinary tract infections	[11]
	Sulfamethoxazole		Approved	Bacterial infections	[12]
	Sulfametopyrazine		Approved	Urinary tract infection	[13]
	Sulfapyridine		Approved	Dermatitis herpetiformis	[9]
	Sulfisoxazole		Approved	Urinary tract infections	[14]
	Sulfonamides		Approved	Bacterial infections	[15]
	Sulphadoxine		Approved	Malaria	[16]
EC Number	EC 2.5.1.15
UniProt ID	P26282
	Q8IAU3
	Q93RQ9
	Q96W63
	Q9BIX9
PDB Structure	1AJ0; 1AJ2; 1AJZ.
Function	Dhps catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide.
Sequence	MKLFAQGTSLDLSHPHVMGILNVTPDSFSDGGTHNSLIDAVKHANLMINAGATIIDVGGE STRPGAAEVSVEEELQRVIPVVEAIAQRFEVWISVDTSKPEVIRESAKVGAHIINDIRSL SEPGALEAAAETGLPVCLMHMQGNPKTMQEAPKYDDVFAEVNRYFIEQIARCEQAGIAKE KLLLDPGFGFGKNLSHNYSLLARLAEFHHFNLPLLVGMSRKSMIGQLLNVGPSERLSGSL ACAVIAAMQGAHIIRVHDVKETVEAMRVVEATLSAKENKRYE
Target Validation	Click to Find Target Validation Information.
Inhibitor	2,6-diamino-5-nitropyrimidin-4 (3H)-one		[17]
	2,6-diamino-5-nitrosopyrimidin-4 (3H)-one		[17]
	2-amino-8-methyl-7,8-dihydropteridin-4 (3H)-one		[17]
	6-Methylamino-5-Nitroisocytosine		[18]
	Dapsone		[5]
	Pterin-6-Yl-Methyl-Monophosphate		[19]
	Pteroic Acid		[20]
	Sulfacytine		[6]
	Sulfadiazine		[7]
	Sulfadoxine		[8]
	Sulfamerazine		[9]
	Sulfamethazine		[10]
	Sulfamethizole		[11]
	Sulfamethoxazole		[12]
	Sulfametopyrazine		[13]
	Sulfapyridine		[9]
	Sulfisoxazole		[14]
	[Pterin-6-Yl Methanyl]-Phosphonophosphate		[19]
Binder	Sulfonamide		[1]
	Sulfonamides		[15]
	Sulphadoxine		[16]
	Sulphameth oxazole		[21]
Cross References	3D Structure Related Literature On-Line Medical Dictionary
Ref 1	Resistance to trimethoprim and sulfonamides. Vet Res. 2001 May-Aug;32(3-4):261-73. To Reference
Ref 2	Utilization of exogenous folate in the human malaria parasite Plasmodium falciparum and its critical role in antifolate drug synergy. Mol Microbiol. 1999 Jun;32(6):1254-62. To Reference
Ref 3	In vivo selection for a specific genotype of dihydropteroate synthetase of Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment. J Infect Dis. 1998 May;177(5):1429-33. To Reference
Ref 4	Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: dihydropteroate synthase gene in lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine. Eur J Biochem. 1994 Sep 1;224(2):397-405. To Reference
Ref 5	Biochemical and structural characterization of the putative dihydropteroate synthase ortholog Rv1207 of Mycobacterium tuberculosis. FEMS Microbiol Lett. 2008 Oct;287(1):128-35. Epub 2008 Aug 1. To Reference
Ref 6	Sulfacytine in uncomplicated urinary tract infections. Double-blind comparison with sulfisoxazole. Urology. 1976 Mar;7(3):267-71. To Reference
Ref 7	Sulfadiazine/hydroxypropyl-beta-cyclodextrin host-guest system: Characterization, phase-solubility and molecular modeling. Bioorg Med Chem. 2008 May 15;16(10):5788-94. Epub 2008 Mar 27. To Reference
Ref 8	Geographical distribution of amino acid mutations in Plasmodium vivax DHFR and DHPS from malaria endemic areas of Thailand. Am J Trop Med Hyg. 2008 Mar;78(3):462-7. To Reference
Ref 9	A confirmatory method for the simultaneous extraction, separation, identification and quantification of Tetracycline, Sulphonamide, Trimethoprim and Dapsone residues in muscle by ultra-high-performance liquid chromatography-tandem mass spectrometry according to Commission Decision 2002/657/EC. J Chromatogr A. 2009 Jun 9. [Epub ahead of print] To Reference
Ref 10	A new and simple method to determine trace levels of sulfonamides in honey by high performance liquid chromatography with fluorescence detection. J Chromatogr A. 2009 May 29. [Epub ahead of print] To Reference
Ref 11	Inhibition of bioluminescence in Photobacterium phosphoreum by sulfamethizole and its stimulation by thymine. Biochim Biophys Acta. 1990 Jun 26;1017(3):229-34. To Reference
Ref 12	In vitro activities of novel antifolate drug combinations against Plasmodium falciparum and human granulocyte CFUs. Antimicrob Agents Chemother. 1995 Apr;39(4):948-52. To Reference
Ref 13	Plasmodium falciparum dihydrofolate reductase Val-16 and Thr-108 mutation associated with in vivo resistance to antifolate drug: a case study. Indian J Malariol. 2001 Sep-Dec;38(3-4):76-83. To Reference
Ref 14	Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63.Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. To Reference
Ref 15	Has nature already identified all useful antibacterial targets? Curr Opin Microbiol. 2008 Oct;11(5):387-92. Epub 2008 Oct 6. To Reference
Ref 16	The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71. To Reference
Ref 17	J Med Chem. 2010 Jan 14;53(1):166-77.Structural studies of pterin-based inhibitors of dihydropteroate synthase. To Reference
Ref 18	Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 19	Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 20	Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 21	Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40. To Reference

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