1ryw: Difference between revisions

Revision as of 08:04, 3 May 2008

C115S MurA liganded with reaction products

OverviewOverview

MurA (UDP-N-acetylglucosamine enolpyruvyl transferase, EC 2.5.1.7) is an essential enzyme in the biosynthesis of the peptidoglycan layer of the bacterial cell. It provides an attractive template for the design of novel antibiotic drugs and is the target of the naturally occurring antibiotic fosfomycin, which covalently attaches to Cys115 in the active site of the enzyme. Mutations of Cys115 to Asp exist in pathogens such as Mycobacteria or Chlamydia rendering these organisms resistant to fosfomycin. Thus, there is a need for the elucidation of the role of this cysteine in the MurA reaction. We determined the x-ray structure of the C115S mutant of Enterobacter cloacae MurA, which was crystallized in the presence of the substrates of MurA. The structure depicts the product state of the enzyme with enolpyruvyl-UDP-N-acetylglucosamine and inorganic phosphate trapped in the active site. Kinetic analysis revealed that the Cys-to-Ser mutation results in an enzyme that appears to perform a single turnover of the reaction. Opposing the common view of Cys115 as a key residue in the chemical reaction of enolpyruvyl transfer, we now conclude that the wild-type cysteine is essential for product release only. On the basis of a detailed comparison of the product state with the intermediate state and an unliganded state of MurA, we propose that dissociation of the products is an ordered event with inorganic phosphate leaving first. Phosphate departure appears to trigger a suite of conformational changes, which finally leads to opening of the two-domain structure of MurA and the release of the second product enolpyruvyl-UDP-N-acetylglucosamine.

About this StructureAbout this Structure

1RYW is a Single protein structure of sequence from Enterobacter cloacae. Full crystallographic information is available from OCA.

ReferenceReference

Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release., Eschenburg S, Priestman M, Schonbrunn E, J Biol Chem. 2005 Feb 4;280(5):3757-63. Epub 2004 Nov 5. PMID:15531591 Page seeded by OCA on Sat May 3 08:04:54 2008

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OCA

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 [[Image:1ryw.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_1ryw", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ASI:L-ISO-ASPARTATE'>ASI</scene>, <scene name='pdbligand=EPU:URIDINE-DIPHOSPHATE-2(N-ACETYLGLUCOSAMINYL)+BUTYRIC+ACID'>EPU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE= MURA, MURZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 Enterobacter cloacae])
+-->
-|DOMAIN=
+{{STRUCTURE_1ryw|  PDB=1ryw  |  SCENE=  }}
-|RELATEDENTRY=[[1q36|1Q36]], [[1dlg|1DLG]], [[1ejc|1EJC]], [[1ejd|1EJD]], [[1eyn|1EYN]], [[1naw|1NAW]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ryw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ryw OCA], [http://www.ebi.ac.uk/pdbsum/1ryw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ryw RCSB]</span>
-}}
 '''C115S MurA liganded with reaction products'''
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 [[Category: Eschenburg, S.]]
 [[Category: Schonbrunn, E.]]
-[[Category: inside-out alpha-beta barrel]]
+[[Category: Inside-out alpha-beta barrel]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 08:04:54 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:34:59 2008''