7jlr
From Proteopedia
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==Crystal structure of Bacillus subtilis UppS in complex with JPD447== | ==Crystal structure of Bacillus subtilis UppS in complex with JPD447== | ||
| - | <StructureSection load='7jlr' size='340' side='right'caption='[[7jlr]]' scene=''> | + | <StructureSection load='7jlr' size='340' side='right'caption='[[7jlr]], [[Resolution|resolution]] 2.20Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JLR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7jlr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JLR FirstGlance]. <br> |
| - | </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=7jlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jlr OCA], [https://pdbe.org/7jlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jlr RCSB], [https://www.ebi.ac.uk/pdbsum/7jlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jlr ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V0D:7-(azepan-1-yl)-5-ethyl-3-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine'>V0D</scene></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=7jlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jlr OCA], [https://pdbe.org/7jlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jlr RCSB], [https://www.ebi.ac.uk/pdbsum/7jlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jlr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ISPT_BACSU ISPT_BACSU] Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[HAMAP-Rule:MF_01139] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The polyprenyl lipid undecaprenyl phosphate (C55P) is the universal carrier lipid for the biosynthesis of bacterial cell wall polymers. C55P is synthesized in its pyrophosphate form by undecaprenyl pyrophosphate synthase (UppS), an essential cis-prenyltransferase that is an attractive target for antibiotic development. We previously identified a compound (MAC-0547630) that showed promise as a novel class of inhibitor and an ability to potentiate beta-lactam antibiotics. Here, we provide a structural model for MAC-0547630's inhibition of UppS and a structural rationale for its enhanced effect on UppS from Bacillus subtilis versus Staphylococcus aureus. We also describe the synthesis of a MAC-0547630 derivative (JPD447), show that it too can potentiate beta-lactam antibiotics, and provide a structural rationale for its improved potentiation. Finally, we present an improved structural model of clomiphene's inhibition of UppS. Taken together, our data provide a foundation for structure-guided drug design of more potent UppS inhibitors in the future. | ||
| + | |||
| + | Structural Insights into the Inhibition of Undecaprenyl Pyrophosphate Synthase from Gram-Positive Bacteria.,Workman SD, Day J, Farha MA, El Zahed SS, Bon C, Brown ED, Organ MG, Strynadka NCJ J Med Chem. 2021 Sep 2. doi: 10.1021/acs.jmedchem.1c00941. PMID:34473495<ref>PMID:34473495</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7jlr" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Undecaprenyl pyrophosphate synthase|Undecaprenyl pyrophosphate synthase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacillus subtilis]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Strynadka NCJ]] | [[Category: Strynadka NCJ]] | ||
[[Category: Workman SD]] | [[Category: Workman SD]] | ||
Current revision
Crystal structure of Bacillus subtilis UppS in complex with JPD447
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