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1ybg
From Proteopedia
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|PDB= 1ybg |SIZE=350|CAPTION= <scene name='initialview01'>1ybg</scene>, resolution 2.6Å | |PDB= 1ybg |SIZE=350|CAPTION= <scene name='initialview01'>1ybg</scene>, resolution 2.6Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=TAV:N-METHYL-N-{2-[(2-NAPHTHYLSULFONYL)AMINO]-5-[(2-NAPHTHYLSULFONYL)OXY]BENZOYL}-L-ASPARTIC ACID'>TAV</scene> | + | |LIGAND= <scene name='pdbligand=ASI:L-ISO-ASPARTATE'>ASI</scene>, <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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= murA, murZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 Enterobacter cloacae]) | |GENE= murA, murZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 Enterobacter cloacae]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1naw|1NAW]], [[1ejd|1EJD]], [[1q3g|1Q3G]], [[1eyn|1EYN]], [[1ejc|1EJC]], [[1uae|1UAE]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ybg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ybg OCA], [http://www.ebi.ac.uk/pdbsum/1ybg PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ybg RCSB]</span> | ||
}} | }} | ||
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[[Category: Priestman, M A.]] | [[Category: Priestman, M A.]] | ||
[[Category: Schonbrunn, E.]] | [[Category: Schonbrunn, E.]] | ||
| - | [[Category: TAV]] | ||
[[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 01:01:59 2008'' |
Revision as of 22:02, 30 March 2008
| |||||||
| , resolution 2.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | murA, murZ (Enterobacter cloacae) | ||||||
| Activity: | UDP-N-acetylglucosamine 1-carboxyvinyltransferase, with EC number 2.5.1.7 | ||||||
| Related: | 1NAW, 1EJD, 1Q3G, 1EYN, 1EJC, 1UAE
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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