4q9o
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4q9o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q9O FirstGlance]. <br> | <table><tr><td colspan='2'>[[4q9o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q9O FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ZW:3-(2-CHLOROPHENYL)-5-METHYL-N-[4-(PROPAN-2-YL)PHENYL]-1,2-OXAZOLE-4-CARBOXAMIDE'>2ZW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2ZW:3-(2-CHLOROPHENYL)-5-METHYL-N-[4-(PROPAN-2-YL)PHENYL]-1,2-OXAZOLE-4-CARBOXAMIDE'>2ZW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4q9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9o OCA], [https://pdbe.org/4q9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q9o RCSB], [https://www.ebi.ac.uk/pdbsum/4q9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q9o ProSAT]</span></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=4q9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q9o OCA], [https://pdbe.org/4q9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q9o RCSB], [https://www.ebi.ac.uk/pdbsum/4q9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q9o ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ISPT_STRR6 ISPT_STRR6] Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[HAMAP-Rule:MF_01139] | [https://www.uniprot.org/uniprot/ISPT_STRR6 ISPT_STRR6] 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 == | ||
| - | Undecaprenyl pyrophosphate synthase (UPPs) is an essential enzyme in a key bacterial cell wall synthesis pathway. It catalyzes the consecutive condensations of isopentenyl pyrophosphate (IPP) groups onto a trans-farnesyl pyrophosphate (FPP) to produce a C55 isoprenoid, undecaprenyl pyrophosphate (UPP). Here we report the discovery and co-crystal structures of a drug-like UPPs inhibitor in complex with Streptococcus pneumoniae UPPs, with and without substrate FPP, at resolutions of 2.2 and 2.1 A, respectively. The UPPs inhibitor has a low molecular weight (355 Da), but displays potent inhibition of UPP synthesis in vitro (IC50 50 nM) that translates into excellent whole cell antimicrobial activity against pathogenic strains of Streptococcal species (MIC90 0.4 mug/mL). Interestingly, the inhibitor does not compete with the substrates but rather binds at a site adjacent to the FPP binding site and interacts with the tail of the substrate. Based on the structures, an allosteric inhibition mechanism of UPPs is proposed for this inhibitor. This inhibition mechanism is supported by biochemical and biophysical experiments, and provides a basis for the development of novel antibiotics targeting Streptococcus pneumoniae. | ||
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| - | Discovery and structural characterization of an allosteric inhibitor of bacterial cis-prenyltransferase.,Danley DE, Baima ET, Mansour M, Fennell KF, Chrunyk BA, Mueller JP, Liu S, Qiu X Protein Sci. 2014 Oct 6. doi: 10.1002/pro.2579. PMID:25287857<ref>PMID:25287857</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4q9o" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of Upps + inhibitor
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