2e90: Difference between revisions

Revision as of 02:09, 4 May 2008

S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with magnesium, pyrophosphate and FPP

OverviewOverview

Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Here, we show that some bisphosphonates can also inhibit geranylgeranyl diphosphate synthase (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a cis-prenyltransferase of interest as a target for antibacterial therapy. Our results on GGPPS (10 structures) show that there are three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate substrate-binding sites together with a GGPP product- or inhibitor-binding site. In UPPS, there are a total of four binding sites (in five structures). These results are of general interest because they provide the first structures of GGPPS- and UPPS-inhibitor complexes, potentially important drug targets, in addition to revealing a remarkably broad spectrum of binding modes not seen in FPPS inhibition.

About this StructureAbout this Structure

2E90 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

ReferenceReference

Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases., Guo RT, Cao R, Liang PH, Ko TP, Chang TH, Hudock MP, Jeng WY, Chen CK, Zhang Y, Song Y, Kuo CJ, Yin F, Oldfield E, Wang AH, Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10022-7. Epub 2007 May 29. PMID:17535895 Page seeded by OCA on Sun May 4 02:09:51 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:2e90.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2e90 |SIZE=350|CAPTION= <scene name='initialview01'>2e90</scene>, resolution 2.55&Aring;
+The line below this paragraph, containing "STRUCTURE_2e90", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPV:PYROPHOSPHATE'>PPV</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Trans-hexaprenyltranstransferase Trans-hexaprenyltranstransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.30 2.5.1.30] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2e90|  PDB=2e90  |  SCENE=  }}
-|RELATEDENTRY=[[2dh4|2DH4]], [[2e8t|2E8T]], [[2e8u|2E8U]], [[2e8v|2E8V]], [[2e8w|2E8W]], [[2e8x|2E8X]], [[2e91|2E91]], [[2e92|2E92]], [[2e93|2E93]], [[2e94|2E94]], [[2e95|2E95]], [[2e96|2E96]], [[2e97|2E97]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e90 OCA], [http://www.ebi.ac.uk/pdbsum/2e90 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2e90 RCSB]</span>
-}}
 '''S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with magnesium, pyrophosphate and FPP'''
@@ Line 34: / Line 31: @@
 [[Category: Oldfield, E.]]
 [[Category: Wang, A H.J.]]
-[[Category: bisphosphonate]]
+[[Category: Bisphosphonate]]
-[[Category: farnesyl pyrophosphate]]
+[[Category: Farnesyl pyrophosphate]]
-[[Category: prenyltransferase]]
+[[Category: Prenyltransferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 02:09:51 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:45:31 2008''