3kr6

From Proteopedia

(Difference between revisions)

Revision as of 19:32, 4 August 2016

MurA dead-end complex with fosfomycin

Structural highlights

3kr6 is a 1 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	3kqa, 3kqj
Gene:	b3189, JW3156, murA, MurA (MurZ), murZ (ECOLI)
Activity:	UDP-N-acetylglucosamine 1-carboxyvinyltransferase, with EC number 2.5.1.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MURA_ECOLI] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic phosphomycin.[HAMAP-Rule:MF_00111]

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 PubMed

Terreic acid is a metabolite with antibiotic properties produced by the fungus Aspergillus terreus. We found that terreic acid is a covalent inhibitor of the bacterial cell wall biosynthetic enzyme MurA from Enterobacter cloacae and Escherichia coli in vitro. The crystal structure of the MurA dead-end complex with terreic acid revealed that the quinine ring is covalently attached to the thiol group of Cys115, the molecular target of the antibiotic fosfomycin. Kinetic characterization established that the inactivation requires the presence of substrate UNAG (UDP-N-acetylglucosamine), proceeding with an inactivation rate constant k(inact) of 130 M(-1) s(-1). Although the mechanisms of inactivation are similar, fosfomycin is approximately 50 times more potent than terreic acid, and the structural consequences of covalent modification by these two inhibitors are fundamentally different. The MurA-fosfomycin complex exists in the closed enzyme conformation, with the Cys115-fosfomycin adduct buried in the active site. In contrast, the dead-end complex with terreic acid is open, is free of UNAG, and has the Cys115-terreic acid adduct solvent-exposed. It appears that terreic acid reacts with Cys115 in the closed, binary state of the enzyme, but that the resulting Cys115-terreic acid adduct imposes steric clashes in the active site. As a consequence, the loop containing Cys115 rearranges, the enzyme opens, and UNAG is released. The differential kinetic and structural characteristics of MurA inactivation by terreic acid and fosfomycin reflect the importance of noncovalent binding potential, even for covalent inhibitors, in ensuring inactivation efficiency and specificity.

The Fungal Product Terreic Acid Is a Covalent Inhibitor of the Bacterial Cell Wall Biosynthetic Enzyme UDP-N-Acetylglucosamine 1-Carboxyvinyltransferase (MurA) .,Han H, Yang Y, Olesen SH, Becker A, Betzi S, Schonbrunn E Biochemistry. 2010 Apr 21. PMID:20392080^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Han H, Yang Y, Olesen SH, Becker A, Betzi S, Schonbrunn E. The Fungal Product Terreic Acid Is a Covalent Inhibitor of the Bacterial Cell Wall Biosynthetic Enzyme UDP-N-Acetylglucosamine 1-Carboxyvinyltransferase (MurA) . Biochemistry. 2010 Apr 21. PMID:20392080 doi:10.1021/bi100365b

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3kr6"

@@ Line 1: / Line 1: @@
 ==MurA dead-end complex with fosfomycin==
 <StructureSection load='3kr6' size='340' side='right' caption='[[3kr6]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3kr6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KR6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KR6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3kr6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KR6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KR6 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FFQ:[(1R)-1-HYDROXYPROPYL]PHOSPHONIC+ACID'>FFQ</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kqa|3kqa]], [[3kqj|3kqj]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b3189, JW3156, murA, MurA (MurZ), murZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b3189, JW3156, murA, MurA (MurZ), murZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=3kr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kr6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kr6 RCSB], [http://www.ebi.ac.uk/pdbsum/3kr6 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=3kr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kr6 OCA], [http://pdbe.org/3kr6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kr6 RCSB], [http://www.ebi.ac.uk/pdbsum/3kr6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kr6 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 21: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kr6 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 30: / Line 31: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3kr6" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 37: / Line 39: @@
 __TOC__
 </StructureSection>
-[[Category: Escherichia coli]]
+[[Category: Ecoli]]
 [[Category: UDP-N-acetylglucosamine 1-carboxyvinyltransferase]]
 [[Category: Schonbrunn, E]]

3kr6

From Proteopedia

Revision as of 19:32, 4 August 2016

MurA dead-end complex with fosfomycin

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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