1x8r
From Proteopedia
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| - | [[Image:1x8r.gif|left|200px]] | + | [[Image:1x8r.gif|left|200px]] |
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| - | '''EPSPS liganded with the (S)-phosphonate analog of the tetrahedral reaction intermediate''' | + | {{Structure |
| + | |PDB= 1x8r |SIZE=350|CAPTION= <scene name='initialview01'>1x8r</scene>, resolution 1.5Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SC1:[3R-[3A,4A,5B(S*)]]-5-(1-CARBOXY-1-PHOSPHONOETHOXY)-4-HYDROXY-3-(PHOSPHONOOXY)-1-CYCLOHEXENE-1-CARBOXYLIC+ACID'>SC1</scene> and <scene name='pdbligand=FMT:FORMIC ACID'>FMT</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= aroA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
| + | }} | ||
| + | |||
| + | '''EPSPS liganded with the (S)-phosphonate analog of the tetrahedral reaction intermediate''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1X8R is a [ | + | 1X8R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X8R OCA]. |
==Reference== | ==Reference== | ||
| - | Interaction of phosphonate analogues of the tetrahedral reaction intermediate with 5-enolpyruvylshikimate-3-phosphate synthase in atomic detail., Priestman MA, Healy ML, Becker A, Alberg DG, Bartlett PA, Lushington GH, Schonbrunn E, Biochemistry. 2005 Mar 8;44(9):3241-8. PMID:[http:// | + | Interaction of phosphonate analogues of the tetrahedral reaction intermediate with 5-enolpyruvylshikimate-3-phosphate synthase in atomic detail., Priestman MA, Healy ML, Becker A, Alberg DG, Bartlett PA, Lushington GH, Schonbrunn E, Biochemistry. 2005 Mar 8;44(9):3241-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15736934 15736934] |
[[Category: 3-phosphoshikimate 1-carboxyvinyltransferase]] | [[Category: 3-phosphoshikimate 1-carboxyvinyltransferase]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
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[[Category: inside-out alpha-beta barrel]] | [[Category: inside-out alpha-beta barrel]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:06:29 2008'' |
Revision as of 13:06, 20 March 2008
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| , resolution 1.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | aroA (Escherichia coli) | ||||||
| Activity: | 3-phosphoshikimate 1-carboxyvinyltransferase, with EC number 2.5.1.19 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
EPSPS liganded with the (S)-phosphonate analog of the tetrahedral reaction intermediate
Overview
The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes the penultimate step of the shikimate pathway and is the target of the broad-spectrum herbicide glyphosate. Since the functionality of the shikimate pathway is vital not only for plants but also for microorganisms, EPSPS is considered a prospective target for the development of novel antibiotics. We have kinetically analyzed and determined the crystal structures of Escherichia coli EPSPS inhibited by (R)- and (S)-configured phosphonate analogues of the tetrahedral reaction intermediate. Both diastereomers are competitive inhibitors with respect to the substrates of the EPSPS reaction, shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP). Remarkably, the (S)-phosphonate (K(iS3P) = 750 nM), whose configuration corresponds to that of the genuine tetrahedral intermediate, is a much weaker inhibitor than the (R)-phosphonate analogue (K(iS3P) = 16 nM). The crystal structures of EPSPS liganded with the (S)- and (R)-phosphonates, at 1.5 and 1.9 A resolution, respectively, revealed that binding of the (R)-phosphonate induces conformational changes of the strictly conserved residues Arg124 and Glu341 within the active site. This appears to give rise to substantial structural alterations in the amino-terminal globular domain of the enzyme. By contrast, binding of the (S)-phosphonate renders the enzyme structure unchanged. Thus, EPSPS may facilitate the tight binding of structurally diverse ligands through conformational flexibility. Molecular docking calculations did not explain why the (R)-phosphonate is the better inhibitor. Therefore, we propose that the structural events during the open-closed transition of EPSPS are altered as a result of inhibitor action.
About this Structure
1X8R is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Interaction of phosphonate analogues of the tetrahedral reaction intermediate with 5-enolpyruvylshikimate-3-phosphate synthase in atomic detail., Priestman MA, Healy ML, Becker A, Alberg DG, Bartlett PA, Lushington GH, Schonbrunn E, Biochemistry. 2005 Mar 8;44(9):3241-8. PMID:15736934
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