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2q80

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[[Image:2q80.jpg|left|200px]]<br /><applet load="2q80" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2q80, resolution 2.70&Aring;" />
 
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'''Crystal structure of human geranylgeranyl pyrophosphate synthase bound to GGPP'''<br />
 
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==Overview==
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==Crystal structure of human geranylgeranyl pyrophosphate synthase bound to GGPP==
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Modification of GTPases with isoprenoid molecules derived from geranylgeranyl pyrophosphate or farnesyl pyrophosphate is an essential requisite for cellular signaling pathways. The synthesis of these isoprenoids proceeds in mammals through the mevalonate pathway, and the final steps in the synthesis are catalyzed by the related enzymes farnesyl pyrophosphate synthase and geranylgeranyl pyrophosphate synthase. Both enzymes play crucial roles in cell survival, and inhibition of farnesyl pyrophosphate synthase by nitrogen-containing bisphosphonates is an established concept in the treatment of bone disorders such as osteoporosis or certain forms of cancer in bone. Here we report the crystal structure of human geranylgeranyl pyrophosphate synthase, the first mammalian ortholog to have its x-ray structure determined. It reveals that three dimers join together to form a propeller-bladed hexameric molecule with a mass of approximately 200 kDa. Structure-based sequence alignments predict this quaternary structure to be restricted to mammalian and insect orthologs, whereas fungal, bacterial, archaeal, and plant forms exhibit the dimeric organization also observed in farnesyl pyrophosphate synthase. Geranylgeranyl pyrophosphate derived from heterologous bacterial expression is tightly bound in a cavity distinct from the chain elongation site described for farnesyl pyrophosphate synthase. The structure most likely represents an inhibitory complex, which is further corroborated by steady-state kinetics, suggesting a possible feedback mechanism for regulating enzyme activity. Structural comparisons between members of this enzyme class give deeper insights into conserved features important for catalysis.
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<StructureSection load='2q80' size='340' side='right'caption='[[2q80]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2q80]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2fvi 2fvi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q80 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]] 2.7&#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=GRG:GERANYLGERANYL+DIPHOSPHATE'>GRG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2q80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q80 OCA], [https://pdbe.org/2q80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q80 RCSB], [https://www.ebi.ac.uk/pdbsum/2q80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q80 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GGPPS_HUMAN GGPPS_HUMAN] Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.
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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/q8/2q80_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=2q80 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2Q80 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GRG:'>GRG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 2FVI. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q80 OCA].
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*[[Geranylgeranyl pyrophosphate synthase 3D structures|Geranylgeranyl pyrophosphate synthase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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The crystal structure of human geranylgeranyl pyrophosphate synthase reveals a novel hexameric arrangement and inhibitory product binding., Kavanagh KL, Dunford JE, Bunkoczi G, Russell RG, Oppermann U, J Biol Chem. 2006 Aug 4;281(31):22004-12. Epub 2006 May 11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16698791 16698791]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith, C.]]
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[[Category: Arrowsmith C]]
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[[Category: Bunkoczi, G.]]
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[[Category: Bunkoczi G]]
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[[Category: Dunford, J E.]]
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[[Category: Dunford JE]]
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[[Category: Edwards, A.]]
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[[Category: Edwards A]]
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[[Category: Kavanagh, K L.]]
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[[Category: Kavanagh KL]]
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[[Category: Oppermann, U.]]
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[[Category: Oppermann U]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Smee C]]
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[[Category: Smee, C.]]
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[[Category: Sundstrom M]]
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[[Category: Sundstrom, M.]]
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[[Category: Weigelt J]]
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[[Category: Vondelft, F.]]
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[[Category: Von Delft F]]
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[[Category: Weigelt, J.]]
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[[Category: GRG]]
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[[Category: MG]]
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[[Category: isopentenyl transferase]]
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[[Category: isoprenoid pathway]]
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[[Category: sgc]]
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[[Category: structural genomics]]
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[[Category: structural genomics consortium]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:36:58 2008''
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Current revision

Crystal structure of human geranylgeranyl pyrophosphate synthase bound to GGPP

PDB ID 2q80

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