1ybg
From Proteopedia
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| - | [[Image:1ybg.gif|left|200px]] | + | [[Image:1ybg.gif|left|200px]] |
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| - | '''MurA inhibited by a derivative of 5-sulfonoxy-anthranilic acid''' | + | {{Structure |
| + | |PDB= 1ybg |SIZE=350|CAPTION= <scene name='initialview01'>1ybg</scene>, resolution 2.6Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=TAV:N-METHYL-N-{2-[(2-NAPHTHYLSULFONYL)AMINO]-5-[(2-NAPHTHYLSULFONYL)OXY]BENZOYL}-L-ASPARTIC ACID'>TAV</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/UDP-N-acetylglucosamine_1-carboxyvinyltransferase UDP-N-acetylglucosamine 1-carboxyvinyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.7 2.5.1.7] | ||
| + | |GENE= murA, murZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 Enterobacter cloacae]) | ||
| + | }} | ||
| + | |||
| + | '''MurA inhibited by a derivative of 5-sulfonoxy-anthranilic acid''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YBG is a [ | + | 1YBG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YBG OCA]. |
==Reference== | ==Reference== | ||
| - | A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA)., Eschenburg S, Priestman MA, Abdul-Latif FA, Delachaume C, Fassy F, Schonbrunn E, J Biol Chem. 2005 Apr 8;280(14):14070-5. Epub 2005 Feb 8. PMID:[http:// | + | A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA)., Eschenburg S, Priestman MA, Abdul-Latif FA, Delachaume C, Fassy F, Schonbrunn E, J Biol Chem. 2005 Apr 8;280(14):14070-5. Epub 2005 Feb 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15701635 15701635] |
[[Category: Enterobacter cloacae]] | [[Category: Enterobacter cloacae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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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 15:20:44 2008'' |
Revision as of 13:20, 20 March 2008
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| , resolution 2.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | murA, murZ (Enterobacter cloacae) | ||||||
| Activity: | UDP-N-acetylglucosamine 1-carboxyvinyltransferase, with EC number 2.5.1.7 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
MurA inhibited by a derivative of 5-sulfonoxy-anthranilic acid
Overview
MurA (UDP-N-acetylglucosamine enolpyruvyl transferase, EC 2.5.1.7) catalyzes the first committed step in the synthesis of the bacterial cell wall. It is the target of the naturally occurring, broad-spectrum antibiotic fosfomycin. Fosfomycin, an epoxide, is a relatively poor drug because an ever-increasing number of bacteria have developed resistance to fosfomycin. Thus, there is a critical need for the development of novel drugs that target MurA by a different molecular mode of action. We have identified a new scaffold of potent MurA inhibitors, derivatives of 5-sulfonoxy-anthranilic acid, using high-throughput screening. T6361 and T6362 are competitive inhibitors of MurA with respect to the first substrate, UDP-N-acetylglucosamine (UNAG), with a K(i) of 16 microM. The crystal structure of the MurA.T6361 complex at 2.6 angstrom resolution, together with fluorescence data, revealed that the inhibitor targets a loop, Pro112 to Pro121, that is crucial for the structural changes of the enzyme during catalysis. Thus, this new class of MurA inhibitors is not active site-directed but instead obstructs the transition from the open (unliganded) to the closed (UNAG-liganded) enzyme form. The results provide evidence for the existence of a MurA.UNAG collision complex that may be specifically targeted by small molecules different from ground-state analogs of the enzymatic reaction.
About this Structure
1YBG is a Single protein structure of sequence from Enterobacter cloacae. Full crystallographic information is available from OCA.
Reference
A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA)., Eschenburg S, Priestman MA, Abdul-Latif FA, Delachaume C, Fassy F, Schonbrunn E, J Biol Chem. 2005 Apr 8;280(14):14070-5. Epub 2005 Feb 8. PMID:15701635
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