3n5h

<StructureSection load='3n5h' size='340' side='right' caption='[[3n5h]], [[Resolution|resolution]] 2.20&Aring;' scene=''>

<table><tr><td colspan='2'>[[3n5h]] 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=3N5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N5H FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GO0:3-(CARBOXYMETHYL)-4,7-DICHLORO-1H-INDOLE-2-CARBOXYLIC+ACID'>GO0</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n1v|3n1v]], [[3n1w|3n1w]], [[3n3l|3n3l]], [[3n45|3n45]], [[3n46|3n46]], [[3n49|3n49]], [[3n5j|3n5j]], [[3n6k|3n6k]]</td></tr>

<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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5h OCA], [http://pdbe.org/3n5h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n5h RCSB], [http://www.ebi.ac.uk/pdbsum/3n5h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n5h ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/FPPS_HUMAN 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.

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n5/3n5h_consurf.spt"</scriptWhenChecked>

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== Publication Abstract from PubMed ==

Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and are highly efficacious in the treatment of bone diseases such as osteoporosis, Paget's disease and tumor-induced osteolysis. In addition, the potential for direct antitumor effects has been postulated on the basis of in vitro and in vivo studies and has recently been demonstrated clinically in early breast cancer patients treated with the potent bisphosphonate zoledronic acid. However, the high affinity of bisphosphonates for bone mineral seems suboptimal for the direct treatment of soft-tissue tumors. Here we report the discovery of the first potent non-bisphosphonate FPPS inhibitors. These new inhibitors bind to a previously unknown allosteric site on FPPS, which was identified by fragment-based approaches using NMR and X-ray crystallography. This allosteric and druggable pocket allows the development of a new generation of FPPS inhibitors that are optimized for direct antitumor effects in soft tissue.

 

== References ==

[[Category: Human]]

[[Category: Rondeau, J M]]

[[Category: Bisphosphonate]]

[[Category: Fragment-based screening]]

[[Category: Transferase-transferase inhibitor complex]]