1q36
From Proteopedia
(New page: 200px<br /><applet load="1q36" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q36, resolution 1.6Å" /> '''EPSP synthase (Asp313...) |
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| - | [[Image:1q36.gif|left|200px]]<br /><applet load="1q36" size=" | + | [[Image:1q36.gif|left|200px]]<br /><applet load="1q36" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1q36, resolution 1.6Å" /> | caption="1q36, resolution 1.6Å" /> | ||
'''EPSP synthase (Asp313Ala) liganded with tetrahedral reaction intermediate'''<br /> | '''EPSP synthase (Asp313Ala) liganded with tetrahedral reaction intermediate'''<br /> | ||
==Overview== | ==Overview== | ||
| - | UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and | + | UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate-3-phosphate synthase (AroA) constitute the small enzyme family of enolpyruvyl transferases, which catalyze the chemically unusual reaction of enolpyruvyl transfer. MurA catalyzes the first step in the biosynthesis of the bacterial cell wall; AroA is the sixth enzyme of the shikimate pathway leading to the synthesis of aromatic compounds in numerous microorganisms and plants. Because both metabolic pathways are absent from mammals but essential for the growth of microorganisms, MurA and AroA are attractive targets for the development of novel antimicrobial drugs. We have determined the x-ray structures of the D305A mutant of Enterobacter cloacae MurA and the D313A mutant of Escherichia coli AroA, both of which crystallized in the presence of their substrates. The structures depict the tetrahedral reaction intermediate states of the enzymes and prove that, without the aspartate side chain, the overall addition-elimination reaction in both enzymes is halted after the addition step. The presented structures lead to a new view of the catalytic mechanism and, moreover, provide an ideal starting point for the rational design of potent inhibitors of MurA and AroA. |
==About this Structure== | ==About this Structure== | ||
| - | 1Q36 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 SKP and FMT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-phosphoshikimate_1-carboxyvinyltransferase 3-phosphoshikimate 1-carboxyvinyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.19 2.5.1.19] Full crystallographic information is available from [http:// | + | 1Q36 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=SKP:'>SKP</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-phosphoshikimate_1-carboxyvinyltransferase 3-phosphoshikimate 1-carboxyvinyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.19 2.5.1.19] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q36 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Eschenburg, S.]] | [[Category: Eschenburg, S.]] | ||
| - | [[Category: Healy, M | + | [[Category: Healy, M L.]] |
[[Category: Kabsch, W.]] | [[Category: Kabsch, W.]] | ||
[[Category: Schonbrunn, E.]] | [[Category: Schonbrunn, E.]] | ||
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[[Category: inside-out alpha-beta barrel]] | [[Category: inside-out alpha-beta barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:35:21 2008'' |
Revision as of 12:35, 21 February 2008
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EPSP synthase (Asp313Ala) liganded with tetrahedral reaction intermediate
Overview
UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate-3-phosphate synthase (AroA) constitute the small enzyme family of enolpyruvyl transferases, which catalyze the chemically unusual reaction of enolpyruvyl transfer. MurA catalyzes the first step in the biosynthesis of the bacterial cell wall; AroA is the sixth enzyme of the shikimate pathway leading to the synthesis of aromatic compounds in numerous microorganisms and plants. Because both metabolic pathways are absent from mammals but essential for the growth of microorganisms, MurA and AroA are attractive targets for the development of novel antimicrobial drugs. We have determined the x-ray structures of the D305A mutant of Enterobacter cloacae MurA and the D313A mutant of Escherichia coli AroA, both of which crystallized in the presence of their substrates. The structures depict the tetrahedral reaction intermediate states of the enzymes and prove that, without the aspartate side chain, the overall addition-elimination reaction in both enzymes is halted after the addition step. The presented structures lead to a new view of the catalytic mechanism and, moreover, provide an ideal starting point for the rational design of potent inhibitors of MurA and AroA.
About this Structure
1Q36 is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as 3-phosphoshikimate 1-carboxyvinyltransferase, with EC number 2.5.1.19 Full crystallographic information is available from OCA.
Reference
A new view of the mechanisms of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate-3-phosphate synthase (AroA) derived from X-ray structures of their tetrahedral reaction intermediate states., Eschenburg S, Kabsch W, Healy ML, Schonbrunn E, J Biol Chem. 2003 Dec 5;278(49):49215-22. Epub 2003 Sep 16. PMID:13129913
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