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| | <StructureSection load='2e8v' size='340' side='right'caption='[[2e8v]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='2e8v' size='340' side='right'caption='[[2e8v]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2e8v]] 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=2E8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E8V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2e8v]] 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=2E8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E8V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GRG:GERANYLGERANYL+DIPHOSPHATE'>GRG</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]] 1.8Å</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]], [[2e8w|2e8w]], [[2e8x|2e8x]], [[2e90|2e90]], [[2e91|2e91]], [[2e92|2e92]], [[2e93|2e93]], [[2e94|2e94]], [[2e95|2e95]], [[2e96|2e96]], [[2e97|2e97]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GRG:GERANYLGERANYL+DIPHOSPHATE'>GRG</scene></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=2e8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e8v OCA], [https://pdbe.org/2e8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e8v RCSB], [https://www.ebi.ac.uk/pdbsum/2e8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e8v 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=2e8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e8v OCA], [https://pdbe.org/2e8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e8v RCSB], [https://www.ebi.ac.uk/pdbsum/2e8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e8v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | |
| - | [[Category: Heptaprenyl diphosphate synthase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chang, T H]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Chen, C K.M]] | + | [[Category: Chang TH]] |
| - | [[Category: Guo, R T]] | + | [[Category: Chen CK-M]] |
| - | [[Category: Jeng, W Y]] | + | [[Category: Guo RT]] |
| - | [[Category: Ko, T P]] | + | [[Category: Jeng WY]] |
| - | [[Category: Liang, P H]] | + | [[Category: Ko TP]] |
| - | [[Category: Oldfield, E]] | + | [[Category: Liang PH]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Oldfield E]] |
| - | [[Category: Bisphosphonate]]
| + | [[Category: Wang AH-J]] |
| - | [[Category: Farnesyl pyrophosphate]]
| + | |
| - | [[Category: Prenyltransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
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.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jiang Y, Proteau P, Poulter D, Ferro-Novick S. BTS1 encodes a geranylgeranyl diphosphate synthase in Saccharomyces cerevisiae. J Biol Chem. 1995 Sep 15;270(37):21793-9. PMID:7665600
- ↑ Shiflett SL, Vaughn MB, Huynh D, Kaplan J, Ward DM. Bph1p, the Saccharomyces cerevisiae homologue of CHS1/beige, functions in cell wall formation and protein sorting. Traffic. 2004 Sep;5(9):700-10. PMID:15296494 doi:http://dx.doi.org/10.1111/j.1600-0854.2004.00213.x
- ↑ 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. Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10022-7. Epub 2007 May 29. PMID:17535895
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