2e90

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(New page: 200px<br /><applet load="2e90" size="350" color="white" frame="true" align="right" spinBox="true" caption="2e90, resolution 2.55&Aring;" /> '''S. cerevisiae gerany...)
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[[Image:2e90.jpg|left|200px]]<br /><applet load="2e90" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2e90, resolution 2.55&Aring;" />
 
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'''S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with magnesium, pyrophosphate and FPP'''<br />
 
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==Overview==
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==S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with magnesium, pyrophosphate and FPP==
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Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act, primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in, decreased prenylation of small GTPases. Here, we show that some, bisphosphonates can also inhibit geranylgeranyl diphosphate synthase, (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a, cis-prenyltransferase of interest as a target for antibacterial therapy., Our results on GGPPS (10 structures) show that there are three, bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate, substrate-binding sites together with a GGPP product- or inhibitor-binding, site. In UPPS, there are a total of four binding sites (in five, structures). These results are of general interest because they provicd de, the first structures of GGPPS- and UPPS-inhibitor complexes, potentially, important drug targets, in addition to revealing a remarkably broad, spectrum of binding modes not seen in FPPS inhibition.
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<StructureSection load='2e90' size='340' side='right'caption='[[2e90]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2e90]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E90 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPV:PYROPHOSPHATE'>PPV</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2e90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e90 OCA], [https://pdbe.org/2e90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e90 RCSB], [https://www.ebi.ac.uk/pdbsum/2e90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e90 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GGPPS_YEAST GGPPS_YEAST] Catalyzes the trans-addition of the 3 molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate. Required for the membrane attachment of YPT1 and SEC4. May be involved in vesicle trafficking and protein sorting.<ref>PMID:7665600</ref> <ref>PMID:15296494</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/2e90_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2e90 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Here, we show that some bisphosphonates can also inhibit geranylgeranyl diphosphate synthase (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a cis-prenyltransferase of interest as a target for antibacterial therapy. Our results on GGPPS (10 structures) show that there are three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate substrate-binding sites together with a GGPP product- or inhibitor-binding site. In UPPS, there are a total of four binding sites (in five structures). These results are of general interest because they provide the first structures of GGPPS- and UPPS-inhibitor complexes, potentially important drug targets, in addition to revealing a remarkably broad spectrum of binding modes not seen in FPPS inhibition.
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==About this Structure==
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Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.,Guo RT, Cao R, Liang PH, Ko TP, Chang TH, Hudock MP, Jeng WY, Chen CK, Zhang Y, Song Y, Kuo CJ, Yin F, Oldfield E, Wang AH Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10022-7. Epub 2007 May 29. PMID:17535895<ref>PMID:17535895</ref>
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2E90 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=PPV:'>PPV</scene> and <scene name='pdbligand=FPP:'>FPP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trans-hexaprenyltranstransferase Trans-hexaprenyltranstransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.30 2.5.1.30] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E90 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases., Guo RT, Cao R, Liang PH, Ko TP, Chang TH, Hudock MP, Jeng WY, Chen CK, Zhang Y, Song Y, Kuo CJ, Yin F, Oldfield E, Wang AH, Proc Natl Acad Sci U S A. 2007 May 29;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17535895 17535895]
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</div>
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[[Category: Saccharomyces cerevisiae]]
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<div class="pdbe-citations 2e90" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Trans-hexaprenyltranstransferase]]
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[[Category: Chang, T.H.]]
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[[Category: Chen, C.K.M.]]
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[[Category: Guo, R.T.]]
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[[Category: Jeng, W.Y.]]
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[[Category: Ko, T.P.]]
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[[Category: Liang, P.H.]]
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[[Category: Oldfield, E.]]
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[[Category: Wang, A.H.J.]]
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[[Category: FPP]]
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[[Category: MG]]
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[[Category: PPV]]
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[[Category: bisphosphonate]]
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[[Category: farnesyl pyrophosphate]]
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[[Category: prenyltransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:46:55 2008''
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==See Also==
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*[[Geranylgeranyl pyrophosphate synthase 3D structures|Geranylgeranyl pyrophosphate synthase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Saccharomyces cerevisiae]]
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[[Category: Chang TH]]
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[[Category: Chen CK-M]]
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[[Category: Guo RT]]
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[[Category: Jeng WY]]
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[[Category: Ko TP]]
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[[Category: Liang PH]]
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[[Category: Oldfield E]]
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[[Category: Wang AH-J]]

Current revision

S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with magnesium, pyrophosphate and FPP

PDB ID 2e90

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