Target type: molecularfunction
Catalysis of the reaction: 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate. [EC:2.5.1.15]
Dihydropteroate synthase (DHPS) is an enzyme involved in the biosynthesis of tetrahydrofolic acid (THF), a crucial coenzyme essential for various metabolic processes. DHPS catalyzes the condensation reaction between para-aminobenzoic acid (PABA) and dihydropteroate, forming dihydrofolate. This reaction is the second step in the folate synthesis pathway and is a critical target for antibacterial and antimalarial drugs.
The molecular function of DHPS can be described as follows:
1. **Substrate binding:** DHPS binds to both PABA and dihydropteroate, ensuring their proper orientation for the reaction.
2. **Catalysis:** DHPS facilitates the formation of a new carbon-nitrogen bond between PABA and dihydropteroate, generating dihydrofolate. This reaction involves the transfer of a proton from PABA to dihydropteroate, followed by the formation of a covalent bond between the two substrates.
3. **Product release:** Once dihydrofolate is formed, it is released from the enzyme, allowing for further steps in the folate biosynthesis pathway.
The catalytic activity of DHPS is highly specific and is regulated by various factors, including the availability of substrates, the presence of cofactors, and the pH of the environment. DHPS plays a critical role in the survival of many organisms, including bacteria, protozoa, and humans. Its essentiality and unique enzymatic activity make it an attractive target for the development of novel therapeutic agents.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Dihydropteroate synthase | A dihydropteroate synthase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0AC13] | Escherichia coli K-12 |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| sulfamethoxazole | sulfamethoxazole : An isoxazole (1,2-oxazole) compound having a methyl substituent at the 5-position and a 4-aminobenzenesulfonamido group at the 3-position. Sulfamethoxazole: A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p208) | isoxazoles; substituted aniline; sulfonamide; sulfonamide antibiotic | antibacterial agent; antiinfective agent; antimicrobial agent; drug allergen; EC 1.1.1.153 [sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)] inhibitor; EC 2.5.1.15 (dihydropteroate synthase) inhibitor; environmental contaminant; epitope; P450 inhibitor; xenobiotic |
| sulfathiazole | sulfathiazole : A 1,3-thiazole compound having a 4-aminobenzenesulfonamido group at the 2-position. Sulfathiazole: A sulfathiazole compound that is used as a short-acting anti-infective agent. It is no longer commonly used systemically due to its toxicity, but may still be applied topically in combination with other drugs for the treatment of vaginal and skin infections, and is still used in veterinary medicine. | 1,3-thiazoles; substituted aniline; sulfonamide; sulfonamide antibiotic | antiinfective agent; drug allergen; EC 2.5.1.15 (dihydropteroate synthase) inhibitor; environmental contaminant; xenobiotic |
| isocytosine | 2-amino-4-hydroxypyrimidine : An aminopyrimidine in which the pyrimidine ring bears amino and hydroxy substituents at positions 2 and 4, respectively. | aminopyrimidine; pyrimidine nucleobase; pyrimidone | |
| 2-amino-6-hydroxy-8-mercaptopurine |