1aj0: Difference between revisions

Revision as of 10:19, 2 May 2008

CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E. COLI DIHYDROPTEROATE SYNTHASE

OverviewOverview

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 StructureAbout this Structure

1AJ0 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

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 Fri May 2 10:19:52 2008

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OCA

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 [[Image:1aj0.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1aj0 |SIZE=350|CAPTION= <scene name='initialview01'>1aj0</scene>, resolution 2.0&Aring;
+The line below this paragraph, containing "STRUCTURE_1aj0", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=PH2:2-AMINO-6-HYDROXYMETHYL-7,8-DIHYDRO-3H-PTERIDIN-4-ONE'>PH2</scene>, <scene name='pdbligand=SAN:SULFANILAMIDE'>SAN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydropteroate_synthase Dihydropteroate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.15 2.5.1.15] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1aj0|  PDB=1aj0  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1aj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aj0 OCA], [http://www.ebi.ac.uk/pdbsum/1aj0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1aj0 RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E. COLI DIHYDROPTEROATE SYNTHASE'''
@@ Line 32: / Line 29: @@
 [[Category: Somers, D O.]]
 [[Category: Stammers, D K.]]
-[[Category: antibiotic]]
+[[Category: Antibiotic]]
-[[Category: biosynthesis]]
+[[Category: Biosynthesis]]
-[[Category: folate]]
+[[Category: Folate]]
-[[Category: resistance]]
+[[Category: Resistance]]
-[[Category: synthase]]
+[[Category: Synthase]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 10:19:52 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:41:21 2008''