3n45: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 ==Human FPPS complex with FBS_04 and zoledronic acid/MG2+==
-<StructureSection load='3n45' size='340' side='right' caption='[[3n45]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
+<StructureSection load='3n45' size='340' side='right'caption='[[3n45]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3n45]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N45 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N45 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3n45]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N45 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N45 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3N3:(2S)-1-[(BENZYLOXY)CARBONYL]-2,3-DIHYDRO-1H-INDOLE-2-CARBOXYLIC+ACID'>3N3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZOL:ZOLEDRONIC+ACID'>ZOL</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]] 1.88&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n1v|3n1v]], [[3n1w|3n1w]], [[3n3l|3n3l]], [[3n46|3n46]], [[3n49|3n49]], [[3n5h|3n5h]], [[3n5j|3n5j]], [[3n6k|3n6k]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3N3:(2S)-1-[(BENZYLOXY)CARBONYL]-2,3-DIHYDRO-1H-INDOLE-2-CARBOXYLIC+ACID'>3N3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZOL:ZOLEDRONIC+ACID'>ZOL</scene></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 Homo sapiens])</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=3n45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n45 OCA], [https://pdbe.org/3n45 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n45 RCSB], [https://www.ebi.ac.uk/pdbsum/3n45 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n45 ProSAT]</span></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=3n45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n45 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n45 RCSB], [http://www.ebi.ac.uk/pdbsum/3n45 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[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.
+[https://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.
 == 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/n4/3n45_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n4/3n45_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3n45 ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== 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.
-Allosteric non-bisphosphonate FPPS inhibitors identified by fragment-based discovery.,Jahnke W, Rondeau JM, Cotesta S, Marzinzik A, Pelle X, Geiser M, Strauss A, Gotte M, Bitsch F, Hemmig R, Henry C, Lehmann S, Glickman JF, Roddy TP, Stout SJ, Green JR Nat Chem Biol. 2010 Sep;6(9):660-6. Epub 2010 Aug 15. PMID:20711197<ref>PMID:20711197</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
 ==See Also==
-*[[Farnesyl diphosphate synthase|Farnesyl diphosphate synthase]]
+*[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]]
-== References ==
-<references/>
 __TOC__
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Rondeau, J M]]
+[[Category: Large Structures]]
-[[Category: Bisphosphonate]]
+[[Category: Rondeau J-M]]
-[[Category: Cholesterol biosynthesis]]
-[[Category: Fragment-based screening]]
-[[Category: Isoprene biosynthesis]]
-[[Category: Transferase]]
-[[Category: Transferase-transferase inhibiator complex]]
-[[Category: Transferase-transferase inhibitor complex]]