1ryw: Difference between revisions
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<StructureSection load='1ryw' size='340' side='right' caption='[[1ryw]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='1ryw' size='340' side='right' caption='[[1ryw]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1ryw]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[1ryw]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/"aerobacter_cloacae"_(jordan_1890)_bergey_et_al._1923 "aerobacter cloacae" (jordan 1890) bergey et al. 1923]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RYW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RYW FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1q36|1q36]], [[1dlg|1dlg]], [[1ejc|1ejc]], [[1ejd|1ejd]], [[1eyn|1eyn]], [[1naw|1naw]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1q36|1q36]], [[1dlg|1dlg]], [[1ejc|1ejc]], [[1ejd|1ejd]], [[1eyn|1eyn]], [[1naw|1naw]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MURA, MURZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MURA, MURZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 "Aerobacter cloacae" (Jordan 1890) Bergey et al. 1923])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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.rcsb.org/pdb/explore.do?structureId=1ryw RCSB], [http://www.ebi.ac.uk/pdbsum/1ryw PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/1ryw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ryw RCSB], [http://www.ebi.ac.uk/pdbsum/1ryw PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/ | [[http://www.uniprot.org/uniprot/MURA_ENTCC MURA_ENTCC]] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic phosphomycin. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 1ryw" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: UDP-N-acetylglucosamine 1-carboxyvinyltransferase]] | [[Category: UDP-N-acetylglucosamine 1-carboxyvinyltransferase]] | ||
[[Category: Eschenburg, S]] | [[Category: Eschenburg, S]] | ||
Revision as of 19:43, 10 September 2015
C115S MurA liganded with reaction productsC115S MurA liganded with reaction products
Structural highlights
Function[MURA_ENTCC] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic phosphomycin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMurA (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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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