View source for 5zlf


==CRYSTAL STRUCTURE OF OCTAPRENYL PYROPHOSPHATE SYNTHASE FROM ESCHERICHIA COLI WITH ligand BPH-629==
<StructureSection load='5zlf' size='340' side='right'caption='[[5zlf]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zlf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZLF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.845&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B29:[2-(3-DIBENZOFURAN-4-YL-PHENYL)-1-HYDROXY-1-PHOSPHONO-ETHYL]-PHOSPHONIC+ACID'>B29</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5zlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zlf OCA], [https://pdbe.org/5zlf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zlf RCSB], [https://www.ebi.ac.uk/pdbsum/5zlf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zlf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ISPB_ECOLI ISPB_ECOLI] Supplies octaprenyl diphosphate, the precursor for the side chain of the isoprenoid quinones ubiquinone and menaquinone.<ref>PMID:8037730</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We report that alkyl-substituted bisphosphonates have activity against Bacillus anthracis Sterne (0.40 mug/mL), Mycobacterium smegmatis (1.4 mug/mL), Bacillus subtilis (1.0 mug/mL), and Staphylococcus aureus (13 mug/mL). In many cases, there is no effect of serum binding, as well as low activity against a human embryonic kidney cell line. Targeting of isoprenoid biosynthesis is involved with 74 having IC(50) values of approximately 100 nM against heptaprenyl diphosphate synthase and 200 nM against farnesyl diphosphate synthase. B. subtilis growth inhibition was rescued by addition of farnesyl diphosphate, menaquinone-4 (MK-4), or undecaprenyl phosphate (UP), and the combination of MK-4 and UP resulted in a 25x increase in ED(50), indicating targeting of both quinone and cell wall biosynthesis. Clostridioides difficile was inhibited by 74, and since this organism does not synthesize quinones, cell wall biosynthesis is the likely target. We also solved three X-ray structures of inhibitors bound to octaprenyl diphosphate and/or undecaprenyl diphosphate synthases.

Discovery of Lipophilic Bisphosphonates That Target Bacterial Cell Wall and Quinone Biosynthesis.,Malwal SR, Chen L, Hicks H, Qu F, Liu W, Shillo A, Law WX, Zhang J, Chandnani N, Han X, Zheng Y, Chen CC, Guo RT, AbdelKhalek A, Seleem MN, Oldfield E J Med Chem. 2019 Mar 14;62(5):2564-2581. doi: 10.1021/acs.jmedchem.8b01878. Epub , 2019 Feb 21. PMID:30730737<ref>PMID:30730737</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5zlf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Chen CC]]
[[Category: Guo RT]]
[[Category: Han X]]
[[Category: Ko TP]]
[[Category: Liu WD]]
[[Category: Zheng YY]]