3swi: Difference between revisions
No edit summary |
No edit summary Tag: Manual revert |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==E. Cloacae MurA in complex with Enolpyruvyl-UDP-N-acetylgalactosamine and covalent adduct of PEP with CYS115== | ==E. Cloacae MurA in complex with Enolpyruvyl-UDP-N-acetylgalactosamine and covalent adduct of PEP with CYS115== | ||
<StructureSection load='3swi' size='340' side='right' caption='[[3swi]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='3swi' size='340' side='right'caption='[[3swi]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3swi]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3swi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae_subsp._cloacae_ATCC_13047 Enterobacter cloacae subsp. cloacae ATCC 13047]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SWI FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MOE:METHOXY-ETHOXYL'>MOE</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=UD2:URIDINE-DIPHOSPHATE-N-ACETYLGALACTOSAMINE'>UD2</scene>, <scene name='pdbligand=UPN:2-{[(2R,3R,4R,5R,6R)-3-(ACETYLAMINO)-2-{[(S)-{[(R)-{[(2R,3S,4R,5R)-5-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHOXY}(HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-5-HYDROXY-6-(HYDROXYMETHYL)TETRAHYDRO-2H-PYRAN-4-YL]OXY}PROP-2-ENOIC+ACID'>UPN | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MOE:METHOXY-ETHOXYL'>MOE</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=QPA:S-[(1S)-1-CARBOXY-1-(PHOSPHONOOXY)ETHYL]-L-CYSTEINE'>QPA</scene>, <scene name='pdbligand=UD2:URIDINE-DIPHOSPHATE-N-ACETYLGALACTOSAMINE'>UD2</scene>, <scene name='pdbligand=UPN:2-{[(2R,3R,4R,5R,6R)-3-(ACETYLAMINO)-2-{[(S)-{[(R)-{[(2R,3S,4R,5R)-5-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHOXY}(HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-5-HYDROXY-6-(HYDROXYMETHYL)TETRAHYDRO-2H-PYRAN-4-YL]OXY}PROP-2-ENOIC+ACID'>UPN</scene></td></tr> | |||
<tr | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3swi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3swi OCA], [https://pdbe.org/3swi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3swi RCSB], [https://www.ebi.ac.uk/pdbsum/3swi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3swi ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
<table> | [https://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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 15: | Line 16: | ||
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> | 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> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3swi" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Enoylpyruvate transferase|Enoylpyruvate transferase]] | *[[Enoylpyruvate transferase 3D structures|Enoylpyruvate transferase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Enterobacter cloacae]] | [[Category: Enterobacter cloacae subsp. cloacae ATCC 13047]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Schonbrunn | [[Category: Schonbrunn E]] | ||
[[Category: Yang | [[Category: Yang Y]] | ||
[[Category: Zhu | [[Category: Zhu J-Y]] | ||
Latest revision as of 12:41, 30 October 2024
E. Cloacae MurA in complex with Enolpyruvyl-UDP-N-acetylgalactosamine and covalent adduct of PEP with CYS115E. Cloacae MurA in complex with Enolpyruvyl-UDP-N-acetylgalactosamine and covalent adduct of PEP with CYS115
Structural highlights
FunctionMURA_ENTCC Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic phosphomycin. Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||