4h2m: Difference between revisions
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==Structure of E. coli undecaprenyl diphosphate synthase in complex with BPH-1408== | ==Structure of E. coli undecaprenyl diphosphate synthase in complex with BPH-1408== | ||
<StructureSection load='4h2m' size='340' side='right' caption='[[4h2m]], [[Resolution|resolution]] 1.78Å' scene=''> | <StructureSection load='4h2m' size='340' side='right'caption='[[4h2m]], [[Resolution|resolution]] 1.78Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4h2m]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4h2m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H2M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H2M FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0YV:2,2-{BENZENE-1,3-DIYLBIS[ETHYNE-2,1-DIYL(5-BROMOBENZENE-3,1-DIYL)]}DIETHANAMINE'>0YV</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0YV:2,2-{BENZENE-1,3-DIYLBIS[ETHYNE-2,1-DIYL(5-BROMOBENZENE-3,1-DIYL)]}DIETHANAMINE'>0YV</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=4h2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h2m OCA], [https://pdbe.org/4h2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h2m RCSB], [https://www.ebi.ac.uk/pdbsum/4h2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h2m ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/UPPS_ECOLI UPPS_ECOLI] Generates ditrans,octacis-undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP) and farnesyl diphosphate (FPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide.<ref>PMID:12756244</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Oldfield E]] | ||
[[Category: | [[Category: Zhu W]] | ||
Revision as of 10:55, 3 November 2022
Structure of E. coli undecaprenyl diphosphate synthase in complex with BPH-1408Structure of E. coli undecaprenyl diphosphate synthase in complex with BPH-1408
Structural highlights
FunctionUPPS_ECOLI Generates ditrans,octacis-undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP) and farnesyl diphosphate (FPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide.[1] Publication Abstract from PubMedWith the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. We report here the discovery and X-ray crystallographic structures of 10 chemically diverse compounds (benzoic, diketo, and phosphonic acids, as well as a bisamidine and a bisamine) that inhibit bacterial undecaprenyl diphosphate synthase, an essential enzyme involved in cell wall biosynthesis. The inhibitors bind to one or more of the four undecaprenyl diphosphate synthase inhibitor binding sites identified previously, with the most active leads binding to site 4, outside the catalytic center. The most potent leads are active against Staphylococcus aureus [minimal inhibitory concentration (MIC)(90) approximately 0.25 microg/mL], and one potently synergizes with methicillin (fractional inhibitory concentration index = 0.25) and is protective in a mouse infection model. These results provide numerous leads for antibacterial development and open up the possibility of restoring sensitivity to drugs such as methicillin, using combination therapies. Antibacterial drug leads targeting isoprenoid biosynthesis.,Zhu W, Zhang Y, Sinko W, Hensler ME, Olson J, Molohon KJ, Lindert S, Cao R, Li K, Wang K, Wang Y, Liu YL, Sankovsky A, de Oliveira CA, Mitchell DA, Nizet V, McCammon JA, Oldfield E Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):123-8. doi: 10.1073/pnas.1219899110. , Epub 2012 Dec 17. PMID:23248302[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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