Target Information
| Target General Information | Top | |||||
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| Target ID |
T88240
(Former ID: TTDS00237)
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| Target Name |
Bacterial Dihydropteroate synthetase (Bact folP)
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| Synonyms |
folP; H2Pte synthase; Dihydropteroate synthase; Dihydropteroate pyrophosphorylase; DHPS
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| Gene Name |
Bact folP
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 9 Target-related Diseases | + | ||||
| 1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
| 2 | Cystitis [ICD-11: GC00] | |||||
| 3 | Dermatitis herpetiformis [ICD-11: EB44] | |||||
| 4 | Glanders [ICD-11: 1B92] | |||||
| 5 | Gram-positive bacterial infection [ICD-11: 1B74-1F40] | |||||
| 6 | Malaria [ICD-11: 1F40-1F45] | |||||
| 7 | Respiratory infection [ICD-11: CA07-CA4Z] | |||||
| 8 | Rheumatic fever [ICD-11: 1B40] | |||||
| 9 | Urinary tract infection [ICD-11: GC08] | |||||
| Function |
Dhps catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide.
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| BioChemical Class |
Alkyl aryl transferase
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| UniProt ID | ||||||
| EC Number |
EC 2.5.1.15
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| Sequence |
MKLFAQGTSLDLSHPHVMGILNVTPDSFSDGGTHNSLIDAVKHANLMINAGATIIDVGGE
STRPGAAEVSVEEELQRVIPVVEAIAQRFEVWISVDTSKPEVIRESAKVGAHIINDIRSL SEPGALEAAAETGLPVCLMHMQGNPKTMQEAPKYDDVFAEVNRYFIEQIARCEQAGIAKE KLLLDPGFGFGKNLSHNYSLLARLAEFHHFNLPLLVGMSRKSMIGQLLNVGPSERLSGSL ACAVIAAMQGAHIIRVHDVKETVEAMRVVEATLSAKENKRYE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 22 Approved Drugs | + | ||||
| 1 | Cefozopran | Drug Info | Approved | Gram-positive bacterial infection | [1] | |
| 2 | Chlorhexidine | Drug Info | Approved | Bacterial infection | [2] | |
| 3 | Colistimethate | Drug Info | Approved | Respiratory tract infection | [3], [4] | |
| 4 | Colistin | Drug Info | Approved | Pseudomonas infection | [4] | |
| 5 | Daptomycin | Drug Info | Approved | Bacterial infection | [5] | |
| 6 | Doripenem | Drug Info | Approved | Urinary tract infection | [6], [7] | |
| 7 | Faropenem | Drug Info | Approved | Gram-positive bacterial infection | [1] | |
| 8 | Gramicidin D | Drug Info | Approved | Bacterial infection | [8] | |
| 9 | Oritavancin | Drug Info | Approved | Bacterial infection | [4], [7] | |
| 10 | Polymyxin B Sulfate | Drug Info | Approved | Pseudomonas infection | [4], [9] | |
| 11 | Silver sulfadiazine | Drug Info | Approved | Bacterial infection | [4], [10], [11] | |
| 12 | Sulfacytine | Drug Info | Approved | Cystitis | [12], [4] | |
| 13 | Sulfadiazine | Drug Info | Approved | Rheumatic fever | [4] | |
| 14 | Sulfamerazine | Drug Info | Approved | Bacterial infection | [13] | |
| 15 | Sulfamethazine | Drug Info | Approved | Bacterial infection | [14] | |
| 16 | Sulfamethizole | Drug Info | Approved | Urinary tract infection | [5] | |
| 17 | Sulfamethoxazole | Drug Info | Approved | Bacterial infection | [4], [5] | |
| 18 | Sulfanilamide | Drug Info | Approved | Bacterial infection | [15] | |
| 19 | Sulfapyridine | Drug Info | Approved | Dermatitis herpetiformis | [4], [16] | |
| 20 | Sulfisoxazole | Drug Info | Approved | Urinary tract infection | [4] | |
| 21 | Sulfonamides | Drug Info | Approved | Bacterial infection | [17] | |
| 22 | Sulphadoxine | Drug Info | Approved | Malaria | [18], [19] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | Sulfametopyrazine | Drug Info | Withdrawn from market | Urinary tract infection | [20] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Inhibitor | [+] 22 Inhibitor drugs | + | ||||
| 1 | Cefozopran | Drug Info | [1] | |||
| 2 | Doripenem | Drug Info | [1] | |||
| 3 | Faropenem | Drug Info | [1] | |||
| 4 | Oritavancin | Drug Info | [1] | |||
| 5 | Sulfacytine | Drug Info | [26] | |||
| 6 | Sulfadiazine | Drug Info | [27] | |||
| 7 | Sulfamerazine | Drug Info | [28] | |||
| 8 | Sulfamethazine | Drug Info | [29] | |||
| 9 | Sulfamethizole | Drug Info | [30] | |||
| 10 | Sulfamethoxazole | Drug Info | [31], [32] | |||
| 11 | Sulfapyridine | Drug Info | [28] | |||
| 12 | Sulfisoxazole | Drug Info | [34] | |||
| 13 | Sulfametopyrazine | Drug Info | [36] | |||
| 14 | 2,6-diamino-5-nitropyrimidin-4(3H)-one | Drug Info | [37] | |||
| 15 | 2,6-diamino-5-nitrosopyrimidin-4(3H)-one | Drug Info | [37] | |||
| 16 | 2-amino-8-methyl-7,8-dihydropteridin-4(3H)-one | Drug Info | [37] | |||
| 17 | 6-Methylamino-5-Nitroisocytosine | Drug Info | [38] | |||
| 18 | Ethylene diamine | Drug Info | [39] | |||
| 19 | HKI-9924129 | Drug Info | [1] | |||
| 20 | Pterin-6-Yl-Methyl-Monophosphate | Drug Info | [40] | |||
| 21 | Pteroic Acid | Drug Info | [41] | |||
| 22 | [Pterin-6-Yl Methanyl]-Phosphonophosphate | Drug Info | [40] | |||
| Breaker | [+] 1 Breaker drugs | + | ||||
| 1 | Chlorhexidine | Drug Info | [21] | |||
| Binder | [+] 8 Binder drugs | + | ||||
| 1 | Colistimethate | Drug Info | [22] | |||
| 2 | Colistin | Drug Info | [22] | |||
| 3 | Daptomycin | Drug Info | [23] | |||
| 4 | Gramicidin D | Drug Info | [24] | |||
| 5 | Polymyxin B Sulfate | Drug Info | [22] | |||
| 6 | Silver sulfadiazine | Drug Info | [25] | |||
| 7 | Sulfonamides | Drug Info | [17] | |||
| 8 | Sulphadoxine | Drug Info | [18], [35] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Sulfanilamide | Drug Info | [33] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Sulfanilamide | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E. COLI DIHYDROPTEROATE SYNTHASE | PDB:1AJ0 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [42] |
| PDB Sequence |
MKLFAQGTSL
10 DLSHPHVMGI20 LNVTPDSFSD30 GGTHNSLIDA40 VKHANLMINA50 GATIIDVGGE 60 STRPGAAEVS70 VEEELQRVIP80 VVEAIAQRFE90 VWISVDTSKP100 EVIRESAKVG 110 AHIINDIRSL120 SEPGALEAAA130 ETGLPVCLMH140 MQGNPKTMQE150 APKYDDVFAE 160 VNRYFIEQIA170 RCEQAGIAKE180 KLLLDPGFGF190 GKNLSHNYSL200 LARLAEFHHF 210 NLPLLVGMSR220 KSMIGQLLNV230 GPSERLSGSL240 ACAVIAAMQG250 AHIIRVHDVK 260 ETVEAMRVVE270 ATLSAKENKR280 YE
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| Ligand Name: 6-Hydroxymethyl-7,8-Dihydropterin | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E. COLI DIHYDROPTEROATE SYNTHASE | PDB:1AJ0 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [42] |
| PDB Sequence |
MKLFAQGTSL
10 DLSHPHVMGI20 LNVTPDSFSD30 GGTHNSLIDA40 VKHANLMINA50 GATIIDVGGE 60 STRPGAAEVS70 VEEELQRVIP80 VVEAIAQRFE90 VWISVDTSKP100 EVIRESAKVG 110 AHIINDIRSL120 SEPGALEAAA130 ETGLPVCLMH140 MQGNPKTMQE150 APKYDDVFAE 160 VNRYFIEQIA170 RCEQAGIAKE180 KLLLDPGFGF190 GKNLSHNYSL200 LARLAEFHHF 210 NLPLLVGMSR220 KSMIGQLLNV230 GPSERLSGSL240 ACAVIAAMQG250 AHIIRVHDVK 260 ETVEAMRVVE270 ATLSAKENKR280 YE
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019822. | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 064216. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73. | |||||
| REF 6 | 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9. | |||||
| REF 7 | 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. | |||||
| REF 8 | Drug information of Gramicidin D, 2008. eduDrugs. | |||||
| REF 9 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 064028. | |||||
| REF 10 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4126). | |||||
| REF 11 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019608. | |||||
| REF 12 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 017569. | |||||
| REF 13 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 080123. | |||||
| REF 14 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 080123. | |||||
| REF 15 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 088718. | |||||
| REF 16 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 000159. | |||||
| REF 17 | Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92. | |||||
| REF 18 | The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71. | |||||
| REF 19 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018557. | |||||
| REF 20 | Drug information of Sulfametopyrazine, 2008. eduDrugs. | |||||
| REF 21 | The mechanism of action of chlorhexidine. FEMS Microbiol Lett. 1992 Dec 15;79(1-3):211-5. | |||||
| REF 22 | Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999 Sep;33(9):960-7. | |||||
| REF 23 | Structural transitions as determinants of the action of the calcium-dependent antibiotic daptomycin. Chem Biol. 2004 Jul;11(7):949-57. | |||||
| REF 24 | Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles. Biochemistry. 2001 Oct 2;40(39):11676-86. | |||||
| REF 25 | Comparative evaluation of transdermal formulations of norfloxacin with silver sulfadiazine cream, USP, for burn wound healing property. J Burns Wounds. 2006 Jun 7;5:e4. | |||||
| REF 26 | Sulfacytine in uncomplicated urinary tract infections. Double-blind comparison with sulfisoxazole. Urology. 1976 Mar;7(3):267-71. | |||||
| REF 27 | Sulfadiazine/hydroxypropyl-beta-cyclodextrin host-guest system: Characterization, phase-solubility and molecular modeling. Bioorg Med Chem. 2008 May 15;16(10):5788-94. | |||||
| REF 28 | A confirmatory method for the simultaneous extraction, separation, identification and quantification of Tetracycline, Sulphonamide, Trimethoprim an... J Chromatogr A. 2009 Nov 13;1216(46):8110-6. | |||||
| REF 29 | 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 Oct 23;1216(43):7275-80. | |||||
| REF 30 | Inhibition of bioluminescence in Photobacterium phosphoreum by sulfamethizole and its stimulation by thymine. Biochim Biophys Acta. 1990 Jun 26;1017(3):229-34. | |||||
| REF 31 | In vitro activities of novel antifolate drug combinations against Plasmodium falciparum and human granulocyte CFUs. Antimicrob Agents Chemother. 1995 Apr;39(4):948-52. | |||||
| REF 32 | Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40. | |||||
| REF 33 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 34 | Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63. | |||||
| REF 35 | 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. | |||||
| REF 36 | 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. | |||||
| REF 37 | Structural studies of pterin-based inhibitors of dihydropteroate synthase. J Med Chem. 2010 Jan 14;53(1):166-77. | |||||
| REF 38 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 39 | Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8. | |||||
| REF 40 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 41 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 42 | Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase. Nat Struct Biol. 1997 Jun;4(6):490-7. | |||||
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