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1ryw

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[[Image:1ryw.gif|left|200px]]
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{{STRUCTURE_1ryw| PDB=1ryw | SCENE= }}
{{STRUCTURE_1ryw| PDB=1ryw | SCENE= }}
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'''C115S MurA liganded with reaction products'''
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===C115S MurA liganded with reaction products===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15531591}}
==About this Structure==
==About this Structure==
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[[Category: Schonbrunn, E.]]
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Revision as of 05:09, 28 July 2008

Image:1ryw.png

Template:STRUCTURE 1ryw

C115S MurA liganded with reaction products

Template:ABSTRACT PUBMED 15531591

About this Structure

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

Reference

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

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