1aj2: Difference between revisions
New page: left|200px<br /><applet load="1aj2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1aj2, resolution 2.00Å" /> '''CRYSTAL STRUCTURE OF... |
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[[Image:1aj2.gif|left|200px]]<br /><applet load="1aj2" size=" | [[Image:1aj2.gif|left|200px]]<br /><applet load="1aj2" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1aj2, resolution 2.00Å" /> | caption="1aj2, resolution 2.00Å" /> | ||
'''CRYSTAL STRUCTURE OF A BINARY COMPLEX OF E. COLI DIHYDROPTEROATE SYNTHASE'''<br /> | '''CRYSTAL STRUCTURE OF A BINARY COMPLEX OF E. COLI DIHYDROPTEROATE SYNTHASE'''<br /> | ||
==Overview== | ==Overview== | ||
Sulfonamides were amongst the first clinically useful antibacterial agents | 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== | ==About this Structure== | ||
1AJ2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4 and 2PH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1AJ2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=2PH:'>2PH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AJ2 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Achari, A.]] | [[Category: Achari, A.]] | ||
[[Category: Bryant, P | [[Category: Bryant, P K.]] | ||
[[Category: Champness, J | [[Category: Champness, J N.]] | ||
[[Category: Rosemond, J.]] | [[Category: Rosemond, J.]] | ||
[[Category: Somers, D | [[Category: Somers, D O.]] | ||
[[Category: Stammers, D | [[Category: Stammers, D K.]] | ||
[[Category: 2PH]] | [[Category: 2PH]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:45:01 2008'' | ||
Revision as of 12:45, 21 February 2008
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CRYSTAL STRUCTURE OF A BINARY 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
1AJ2 is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Dihydropteroate synthase, with EC number 2.5.1.15 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
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