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1x8r
From Proteopedia
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|PDB= 1x8r |SIZE=350|CAPTION= <scene name='initialview01'>1x8r</scene>, resolution 1.5Å | |PDB= 1x8r |SIZE=350|CAPTION= <scene name='initialview01'>1x8r</scene>, resolution 1.5Å | ||
|SITE= | |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> | + | |LIGAND= <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <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> |
| - | + | |ACTIVITY= <span class='plainlinks'>[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] </span> | |
|GENE= aroA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | |GENE= aroA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1g6s|1G6S]], [[1g6t|1G6T]], [[1mi4|1MI4]], [[1q36|1Q36]], [[1x8t|1X8T]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1x8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x8r OCA], [http://www.ebi.ac.uk/pdbsum/1x8r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1x8r RCSB]</span> | ||
}} | }} | ||
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[[Category: Priestman, M A.]] | [[Category: Priestman, M A.]] | ||
[[Category: Schonbrunn, E.]] | [[Category: Schonbrunn, E.]] | ||
| - | [[Category: FMT]] | ||
| - | [[Category: SC1]] | ||
[[Category: inside-out alpha-beta barrel]] | [[Category: inside-out alpha-beta barrel]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:46:12 2008'' |
Revision as of 21:46, 30 March 2008
| |||||||
| , resolution 1.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | aroA (Escherichia coli) | ||||||
| Activity: | 3-phosphoshikimate 1-carboxyvinyltransferase, with EC number 2.5.1.19 | ||||||
| Related: | 1G6S, 1G6T, 1MI4, 1Q36, 1X8T
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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