5ja0: Difference between revisions
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==Crystal structure of human FPPS with allosterically bound FPP== | ==Crystal structure of human FPPS with allosterically bound FPP== | ||
<StructureSection load='5ja0' size='340' side='right' caption='[[5ja0]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='5ja0' size='340' side='right'caption='[[5ja0]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ja0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JA0 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5ja0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JA0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JA0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><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=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FDPS, FPS, KIAA1293 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ja0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ja0 OCA], [http://pdbe.org/5ja0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ja0 RCSB], [http://www.ebi.ac.uk/pdbsum/5ja0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ja0 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5ja0" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5ja0" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Berghuis, A M]] | [[Category: Berghuis, A M]] | ||
[[Category: Park, J]] | [[Category: Park, J]] | ||
Revision as of 10:39, 10 June 2020
Crystal structure of human FPPS with allosterically bound FPPCrystal structure of human FPPS with allosterically bound FPP
Structural highlights
Function[FPPS_HUMAN] Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate. Publication Abstract from PubMedFarnesyl pyrophosphate synthase (FPPS) is an enzyme of the mevalonate pathway and a well-established therapeutic target. Recent research has focused around a newly identified druggable pocket near the enzyme's active site. Pharmacological exploitation of this pocket is deemed promising; however, its natural biological function, if any, is yet unknown. Here we report that the product of FPPS, farnesyl pyrophosphate (FPP), can bind to this pocket and lock the enzyme in an inactive state. The Kd for this binding is 5-6 muM, within a catalytically relevant range. These results indicate that FPPS activity is sensitive to the product concentration. Kinetic analysis shows that the enzyme is inhibited through FPP accumulation. Having a specific physiological effector, FPPS is a bona fide allosteric enzyme. This allostery offers an exquisite mechanism for controlling prenyl pyrophosphate levels in vivo and thus contributes an additional layer of regulation to the mevalonate pathway. Human farnesyl pyrophosphate synthase is allosterically inhibited by its own product.,Park J, Zielinski M, Magder A, Tsantrizos YS, Berghuis AM Nat Commun. 2017 Jan 18;8:14132. doi: 10.1038/ncomms14132. PMID:28098152[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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