2zev: Difference between revisions

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-[[Image:2zev.png|left|200px]]
-{{STRUCTURE_2zev|  PDB=2zev  |  SCENE=  }}
+==S. Cerevisiae Geranylgeranyl Pyrophosphate Synthase in Complex with Magnesium, IPP and BPH-715==
+<StructureSection load='2zev' size='340' side='right'caption='[[2zev]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2zev]] 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=2ZEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZEV FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.23&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B71:3-(DECYLOXY)-1-(2,2-DIPHOSPHONOETHYL)PYRIDINIUM'>B71</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=2zev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zev OCA], [https://pdbe.org/2zev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zev RCSB], [https://www.ebi.ac.uk/pdbsum/2zev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zev ProSAT]</span></td></tr>
+</table>
+== 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>
+== 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/ze/2zev_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/main_output.php?pdb_ID=2zev ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Considerable effort has focused on the development of selective protein farnesyl transferase (FTase) and protein geranylgeranyl transferase (GGTase) inhibitors as cancer chemotherapeutics. Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Due to dual site targeting and decreased polarity, the compounds have activities far greater than do current bisphosphonate drugs in inhibiting tumor cell growth and invasiveness, both in vitro and in vivo. We explore how these compounds inhibit cell growth and how cell activity can be predicted based on enzyme inhibition data, and using X-ray diffraction, solid state NMR, and isothermal titration calorimetry, we show how these compounds bind to FPPS and/or GGPPS.
-===S. Cerevisiae Geranylgeranyl Pyrophosphate Synthase in Complex with Magnesium, IPP and BPH-715===
+Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation.,Zhang Y, Cao R, Yin F, Hudock MP, Guo RT, Krysiak K, Mukherjee S, Gao YG, Robinson H, Song Y, No JH, Bergan K, Leon A, Cass L, Goddard A, Chang TK, Lin FY, Van Beek E, Papapoulos S, Wang AH, Kubo T, Ochi M, Mukkamala D, Oldfield E J Am Chem Soc. 2009 Apr 15;131(14):5153-62. PMID:19309137<ref>PMID:19309137</ref>
-{{ABSTRACT_PUBMED_19309137}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2zev" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[2zev]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEV OCA].
+*[[Geranylgeranyl pyrophosphate synthase 3D structures|Geranylgeranyl pyrophosphate synthase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:019309137</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Saccharomyces cerevisiae]]
-[[Category: Trans-hexaprenyltranstransferase]]
+[[Category: Cao R]]
-[[Category: Cao, R.]]
+[[Category: Chen CK-M]]
-[[Category: Chen, C K.M.]]
+[[Category: Guo RT]]
-[[Category: Guo, R T.]]
+[[Category: Oldfield E]]
-[[Category: Oldfield, E.]]
+[[Category: Wang AH-J]]
-[[Category: Wang, A H.J.]]
-[[Category: Bisphosphonate]]
-[[Category: Carotenoid biosynthesis]]
-[[Category: Farnesyl pyrophosphate]]
-[[Category: Isoprene biosynthesis]]
-[[Category: Multifunctional enzyme]]
-[[Category: Prenyltransferase]]
-[[Category: Protein transport]]
-[[Category: Transferase]]
-[[Category: Transport]]