1AJ0
CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E. COLI DIHYDROPTEROATE SYNTHASE
Summary for 1AJ0
| Entry DOI | 10.2210/pdb1aj0/pdb |
| Descriptor | DIHYDROPTEROATE SYNTHASE, SULFATE ION, 2-AMINO-6-HYDROXYMETHYL-7,8-DIHYDRO-3H-PTERIDIN-4-ONE, ... (5 entities in total) |
| Functional Keywords | antibiotic, resistance, transferase, folate, biosynthesis, synthase |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 31115.55 |
| Authors | Achari, A.,Somers, D.O.,Champness, J.N.,Bryant, P.K.,Rosemond, J.,Stammers, D.K. (deposition date: 1997-05-14, release date: 1998-05-20, Last modification date: 2024-02-07) |
| Primary citation | Achari, A.,Somers, D.O.,Champness, J.N.,Bryant, P.K.,Rosemond, J.,Stammers, D.K. Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase. Nat.Struct.Biol., 4:490-497, 1997 Cited by PubMed Abstract: Sulfonamides were amongst the first clinically useful antibacterial agents to be discovered. The identification of sulfanilamide as the active component of the dye Prontosil rubrum led to the synthesis of clinically useful analogues. Today sulfamethoxazole (in combination with trimethoprim), is used to treat urinary tract infections caused by bacteria such as Escherichia coli and is also a first-line treatment for pneumonia caused by the fungus Pneumocystis carinii, a common condition in AIDS patients. The site of action is the de novo folate biosynthesis enzyme dihydropteroate synthase (DHPS) where sulfonamides act as analogues of one of the substrates, para-aminobenzoic acid (pABA). We report here the crystal structure of E.coli DHPS at 2.0 A resolution refined to an R-factor of 0.185. The single domain of 282 residues forms an eight-stranded alpha/beta-barrel. The 7,8-dihydropterin pyrophosphate (DHPPP) substrate binds in a deep cleft in the barrel, whilst sulfanilamide binds closer to the surface. The DHPPP ligand site is highly conserved amongst prokaryotic and eukaryotic DHPSs. PubMed: 9187658DOI: 10.1038/nsb0697-490 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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