2pqb
From Proteopedia
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|PDB= 2pqb |SIZE=350|CAPTION= <scene name='initialview01'>2pqb</scene>, resolution 1.800Å | |PDB= 2pqb |SIZE=350|CAPTION= <scene name='initialview01'>2pqb</scene>, resolution 1.800Å | ||
|SITE= <scene name='pdbsite=AC1:Gg9+Binding+Site+For+Residue+A+501'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Gg9+Binding+Site+For+Residue+A+501'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=GG9:'>GG9</scene> | + | |LIGAND= <scene name='pdbligand=GG9:(3R,4S,5R)-5-[(1R)-1-CARBOXY-2,2-DIFLUORO-1-(PHOSPHONOOXY)ETHOXY]-4-HYDROXY-3-(PHOSPHONOOXY)CYCLOHEX-1-ENE-1-CARBOXYLIC+ACID'>GG9</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] | + | |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=361 Agrobacterium sp.]) | |GENE= aroA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=361 Agrobacterium sp.]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2gga|2GGA]], [[2gg6|2GG6]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pqb OCA], [http://www.ebi.ac.uk/pdbsum/2pqb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2pqb RCSB]</span> | ||
}} | }} | ||
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[[Category: Healy-Fried, M L.]] | [[Category: Healy-Fried, M L.]] | ||
[[Category: Schonbrunn, E.]] | [[Category: Schonbrunn, E.]] | ||
| - | [[Category: GG9]] | ||
[[Category: inside-out alpha/beta barrel]] | [[Category: inside-out alpha/beta barrel]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''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 04:39:18 2008'' |
Revision as of 01:39, 31 March 2008
| |||||||
| , resolution 1.800Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| Gene: | aroA (Agrobacterium sp.) | ||||||
| Activity: | 3-phosphoshikimate 1-carboxyvinyltransferase, with EC number 2.5.1.19 | ||||||
| Related: | 2GGA, 2GG6
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CP4 EPSPS liganded with (R)-difluoromethyl tetrahedral intermediate analog
Overview
The shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase or EPSPS) is best known as the target of the herbicide glyphosate. EPSPS is also considered an attractive target for the development of novel antibiotics since the pathogenicity of many microorganisms depends on the functionality of the shikimate pathway. Here, we have investigated the inhibitory potency of stable fluorinated or phosphonate-based analogues of the tetrahedral reaction intermediate (TI) in a parallel study utilizing class I (glyphosate-sensitive) and class II (glyphosate-tolerant) EPSPS. The (R)-difluoromethyl and (R)-phosphonate analogues of the TI are the most potent inhibitors of EPSPS described to date. However, we found that class II EPSPS are up to 400 times less sensitive to inhibition by these TI analogues. X-ray crystallographic data revealed that the conformational changes of active site residues observed upon inhibitor binding to the representative class I EPSPS from Escherichia coli do not occur in the prototypical class II enzyme from Agrobacterium sp. strain CP4. It appears that because the active sites of class II EPSPS do not possess the flexibility to accommodate these TI analogues, the analogues themselves undergo conformational changes, resulting in less favorable inhibitory properties. Since pathogenic microorganisms such as Staphylococcus aureus utilize class II EPSPS, we conclude that the rational design of novel EPSPS inhibitors with potential as broad-spectrum antibiotics should be based on the active site structures of class II EPSP synthases.
About this Structure
2PQB is a Single protein structure of sequence from Agrobacterium sp.. Full crystallographic information is available from OCA.
Reference
Differential inhibition of class I and class II 5-enolpyruvylshikimate-3-phosphate synthases by tetrahedral reaction intermediate analogues., Funke T, Healy-Fried ML, Han H, Alberg DG, Bartlett PA, Schonbrunn E, Biochemistry. 2007 Nov 20;46(46):13344-51. Epub 2007 Oct 25. PMID:17958399
Page seeded by OCA on Mon Mar 31 04:39:18 2008
