1AJZ

STRUCTURE OF DIHYDROPTEROATE PYROPHOSPHORYLASE

Summary for 1AJZ

• Entry DOI: 10.2210/pdb1ajz/pdb
• Descriptor: DIHYDROPTEROATE SYNTHASE, SULFATE ION (3 entities in total)
• Functional Keywords: antibiotic, resistance, transferase, folate, biosynthesis, synthase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 30844.23

Authors

Achari, A.,Somers, D.O.,Champness, J.N.,Bryant, P.K.,Rosemond, J.,Stammers, D.K. (deposition date: 1997-05-13, release date: 1998-05-13, 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

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: 9187658
DOI: 10.1038/nsb0697-490

Experimental method

X-RAY DIFFRACTION (2 Å)