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| | <StructureSection load='4y7t' size='340' side='right'caption='[[4y7t]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4y7t' size='340' side='right'caption='[[4y7t]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4y7t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Psepb Psepb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y7T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y7T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4y7t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_putida_BIRD-1 Pseudomonas putida BIRD-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y7T FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPUBIRD1_0444 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=931281 PSEPB])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4y7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y7t OCA], [https://pdbe.org/4y7t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y7t RCSB], [https://www.ebi.ac.uk/pdbsum/4y7t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y7t ProSAT]</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=4y7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y7t OCA], [http://pdbe.org/4y7t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y7t RCSB], [http://www.ebi.ac.uk/pdbsum/4y7t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y7t ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MURU_PSEPK MURU_PSEPK] Catalyzes the formation of UDP-N-acetylmuramate (UDP-MurNAc), a crucial precursor of the bacterial peptidoglycan cell wall, from UTP and MurNAc-alpha-1P (PubMed:23831760, PubMed:25767118). Is involved in peptidoglycan recycling as part of a cell wall recycling pathway that bypasses de novo biosynthesis of the peptidoglycan precursor UDP-MurNAc (PubMed:23831760). Plays a role in intrinsic resistance to fosfomycin, which targets the de novo synthesis of UDP-MurNAc (PubMed:23831760). Is not able to use GlcNAc-alpha-1P and GalNAc-alpha-1P as substrates (PubMed:23831760). Cannot accept other nucleotide triphosphates (ATP, CTP, TTP, or GTP) than UTP (PubMed:25767118).<ref>PMID:23831760</ref> <ref>PMID:25767118</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Psepb]] | + | [[Category: Pseudomonas putida BIRD-1]] |
| - | [[Category: Renner-Schneck, M G]] | + | [[Category: Renner-Schneck MG]] |
| - | [[Category: Stehle, T]] | + | [[Category: Stehle T]] |
| - | [[Category: Nucleotidyltransferase family protein]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Uridyltransferase]]
| + | |
| Structural highlights
Function
MURU_PSEPK Catalyzes the formation of UDP-N-acetylmuramate (UDP-MurNAc), a crucial precursor of the bacterial peptidoglycan cell wall, from UTP and MurNAc-alpha-1P (PubMed:23831760, PubMed:25767118). Is involved in peptidoglycan recycling as part of a cell wall recycling pathway that bypasses de novo biosynthesis of the peptidoglycan precursor UDP-MurNAc (PubMed:23831760). Plays a role in intrinsic resistance to fosfomycin, which targets the de novo synthesis of UDP-MurNAc (PubMed:23831760). Is not able to use GlcNAc-alpha-1P and GalNAc-alpha-1P as substrates (PubMed:23831760). Cannot accept other nucleotide triphosphates (ATP, CTP, TTP, or GTP) than UTP (PubMed:25767118).[1] [2]
Publication Abstract from PubMed
The N-acetylmuramic acid alpha-1-phosphate (MurNAc-alpha1P) uridylyltransferase MurU catalyzes the synthesis of uridine diphosphate (UDP)-MurNAc, a crucial precursor of the bacterial peptidoglycan cell wall. MurU is part of a recently identified cell wall recycling pathway in Gram-negative bacteria that bypasses the general de-novo biosynthesis of UDP-MurNAc and contributes to high intrinsic resistance to the antibiotic fosfomycin, which targets UDP-MurNAc de novo biosynthesis. To provide insights into substrate binding and specificity, we solved crystal structures of MurU of Pseudomonas putida in native and ligand-bound states at high resolution. With the help of these structures, critical enzyme- substrate interactions were identified that enable tight binding of MurNAc-alpha1P to the active site of MurU. The MurU structures define a "minimal domain" required for general nucleotidyltransferase activity. They furthermore provide a structural basis for the chemical design of inhibitors of MurU, which could serve as novel drugs in combination therapy against multi-resistant Gram-negative pathogens.
Crystal structure of the N-acetylmuramic acid alpha-1-phosphate (MurNAc-alpha1P) uridylytransferase MurU, a minimal sugar-nucleotidyltransferase and potential drug target enzyme in Gram-negative pathogens.,Renner-Schneck M, Hinderberger I, Gisin J, Exner T, Mayer C, Stehle T J Biol Chem. 2015 Mar 12. pii: jbc.M114.620989. PMID:25767118[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gisin J, Schneider A, Nägele B, Borisova M, Mayer C. A cell wall recycling shortcut that bypasses peptidoglycan de novo biosynthesis. Nat Chem Biol. 2013 Aug;9(8):491-3. PMID:23831760 doi:10.1038/nchembio.1289
- ↑ Renner-Schneck M, Hinderberger I, Gisin J, Exner T, Mayer C, Stehle T. Crystal structure of the N-acetylmuramic acid alpha-1-phosphate (MurNAc-alpha1P) uridylytransferase MurU, a minimal sugar-nucleotidyltransferase and potential drug target enzyme in Gram-negative pathogens. J Biol Chem. 2015 Mar 12. pii: jbc.M114.620989. PMID:25767118 doi:http://dx.doi.org/10.1074/jbc.M114.620989
- ↑ Renner-Schneck M, Hinderberger I, Gisin J, Exner T, Mayer C, Stehle T. Crystal structure of the N-acetylmuramic acid alpha-1-phosphate (MurNAc-alpha1P) uridylytransferase MurU, a minimal sugar-nucleotidyltransferase and potential drug target enzyme in Gram-negative pathogens. J Biol Chem. 2015 Mar 12. pii: jbc.M114.620989. PMID:25767118 doi:http://dx.doi.org/10.1074/jbc.M114.620989
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