1ajz

From Proteopedia

Revision as of 09:45, 21 February 2008 by OCA (Talk | contribs)
Jump to: navigation, search

1ajz, resolution 2.00Å

Drag the structure with the mouse to rotate

STRUCTURE OF DIHYDROPTEROATE PYROPHOSPHORYLASE

Overview

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.

About this Structure

1AJZ is a Single protein structure of sequence from Escherichia coli with as ligand. Active as Dihydropteroate synthase, with EC number 2.5.1.15 Full crystallographic information is available from OCA.

Reference

Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase., Achari A, Somers DO, Champness JN, Bryant PK, Rosemond J, Stammers DK, Nat Struct Biol. 1997 Jun;4(6):490-7. PMID:9187658

Page seeded by OCA on Thu Feb 21 11:45:19 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools