3upk: Difference between revisions

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-[[Image:3upk.png|left|200px]]
+==E. cloacae MURA in complex with UNAG==
+<StructureSection load='3upk' size='340' side='right' caption='[[3upk]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3upk]] is a 1 chain structure with 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=3UPK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UPK FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ECL_04571, murA, murZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 Enterobacter cloacae])</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=3upk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3upk RCSB], [http://www.ebi.ac.uk/pdbsum/3upk PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/MURA_ENTCC MURA_ENTCC]] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic phosphomycin.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The enzyme MurA has been an established antibiotic target since the discovery of fosfomycin, which specifically inhibits MurA by covalent modification of the active site residue Cys115. Early biochemical studies established that Cys115 also covalently reacts with substrate phosphoenolpyruvate (PEP) to yield a phospholactoyl adduct, but the structural and functional consequences of this reaction remained obscure. We captured and depicted the Cys115-PEP adduct of E. cloacace MurA in various reaction states by X-ray crystallography. The data suggest that cellular MurA predominantly exists in a tightly locked complex with UDP-N-acetylmuramic acid (UNAM), the product of the MurB reaction, with PEP covalently attached to Cys115. The uniqueness and rigidity of this dormant complex was previously not recognized and presumably accounts for the failure of drug discovery efforts towards the identification of novel and effective MurA inhibitors. We demonstrate that recently published crystal structures of MurA from various organisms determined by different laboratories were indeed misinterpreted and actually contain UNAM and covalently bound PEP. The Cys115-PEP adduct was also captured in vitro during the reaction of free MurA and substrate UDP-N-acetylglucosamine (UNAG) or isomer UDP-N-acetylgalactosamine. The now available series of crystal structures allows a comprehensive view of the reaction cycle of MurA. It appears that the covalent reaction of MurA with PEP fulfills dual functions by tightening the complex with UNAM for the efficient feedback regulation of murein biosynthesis and by priming the PEP molecule for instantaneous reaction with substrate UNAG.
-<!--
+Functional consequence of the covalent reaction of phosphoenolpyruvate with UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA).,Zhu JY, Yang Y, Han H, Betzi S, Olesen S, Marsilio F, Schonbrunn E J Biol Chem. 2012 Feb 29. PMID:22378791<ref>PMID:22378791</ref>
-The line below this paragraph, containing "STRUCTURE_3upk", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_3upk|  PDB=3upk  |  SCENE=  }}
-===E. cloacae MURA in complex with UNAG===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+==See Also==
-<!--
+*[[Enoylpyruvate transferase|Enoylpyruvate transferase]]
-The line below this paragraph, {{ABSTRACT_PUBMED_22378791}}, adds the Publication Abstract to the page
+== References ==
-(as it appears on PubMed at http://www.pubmed.gov), where 22378791 is the PubMed ID number.
+<references/>
--->
+__TOC__
-{{ABSTRACT_PUBMED_22378791}}
+</StructureSection>
-==About this Structure==
-[[3upk]] is a 1 chain structure with 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=3UPK OCA].
-==Reference==
-<ref group="xtra">PMID:022378791</ref><references group="xtra"/>
 [[Category: Enterobacter cloacae]]
 [[Category: UDP-N-acetylglucosamine 1-carboxyvinyltransferase]]
-[[Category: Schonbrunn, E.]]
+[[Category: Schonbrunn, E]]
-[[Category: Yang, Y.]]
+[[Category: Yang, Y]]
-[[Category: Zhu, J Y.]]
+[[Category: Zhu, J Y]]
 [[Category: Biogenesis/degradation]]
 [[Category: Cell wall]]