View source for 2e93


==S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with BPH-629==
<StructureSection load='2e93' size='340' side='right'caption='[[2e93]], [[Resolution|resolution]] 2.12&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2e93]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E93 FirstGlance]. <br>
</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></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2dh4|2dh4]], [[2e8t|2e8t]], [[2e8u|2e8u]], [[2e8v|2e8v]], [[2e8w|2e8w]], [[2e8x|2e8x]], [[2e90|2e90]], [[2e91|2e91]], [[2e92|2e92]], [[2e94|2e94]], [[2e95|2e95]], [[2e96|2e96]], [[2e97|2e97]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Heptaprenyl_diphosphate_synthase Heptaprenyl diphosphate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.30 2.5.1.30] </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=2e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e93 OCA], [https://pdbe.org/2e93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e93 RCSB], [https://www.ebi.ac.uk/pdbsum/2e93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e93 ProSAT]</span></td></tr>
</table>
== Function ==
[[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>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/2e93_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2e93 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2e93" style="background-color:#fffaf0;"></div>

==See Also==
*[[Geranylgeranyl pyrophosphate synthase 3D structures|Geranylgeranyl pyrophosphate synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Atcc 18824]]
[[Category: Heptaprenyl diphosphate synthase]]
[[Category: Large Structures]]
[[Category: Cao, R]]
[[Category: Chang, T H]]
[[Category: Chen, C K.M]]
[[Category: Guo, R T]]
[[Category: Jeng, W Y]]
[[Category: Ko, T P]]
[[Category: Liang, P H]]
[[Category: Oldfield, E]]
[[Category: Wang, A H.J]]
[[Category: Bisphosphonate]]
[[Category: Farnesyl pyrophosphate]]
[[Category: Prenyltransferase]]
[[Category: Transferase]]