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2z7i

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Revision as of 09:07, 17 October 2018

S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with inhibitor BPH-742

Structural highlights

2z7i is a 2 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2z7h
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

We report the X-ray structures of several bisphosphonate inhibitors of geranylgeranyl diphosphate synthase, a target for anticancer drugs. Bisphosphonates containing unbranched side chains bind to either the farnesyl diphosphate (FPP) substrate site, the geranylgeranyl diphosphate (GGPP) product site, and in one case, both sites, with the bisphosphonate moiety interacting with 3 Mg (2+) that occupy the same position as found in FPP synthase. However, each of three "V-shaped" bisphosphonates bind to both the FPP and GGPP sites. Using the Glide program, we reproduced the binding modes of 10 bisphosphonates with an rms error of 1.3 A. Activities of the bisphosphonates in GGPPS inhibition were predicted with an overall error of 2x by using a comparative molecular similarity analysis based on a docked-structure alignment. These results show that some GGPPS inhibitors can occupy both substrate and product site and that binding modes as well as activity can be accurately predicted, facilitating the further development of GGPPS inhibitors as anticancer agents.

Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation.,K-M Chen C, Hudock MP, Zhang Y, Guo RT, Cao R, No JH, Liang PH, Ko TP, Chang TH, Chang SC, Song Y, Axelson J, Kumar A, Wang AH, Oldfield E J Med Chem. 2008 Sep 25;51(18):5594-607. PMID:18800762^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jiang Y, Proteau P, Poulter D, Ferro-Novick S. BTS1 encodes a geranylgeranyl diphosphate synthase in Saccharomyces cerevisiae. J Biol Chem. 1995 Sep 15;270(37):21793-9. PMID:7665600
↑ Shiflett SL, Vaughn MB, Huynh D, Kaplan J, Ward DM. Bph1p, the Saccharomyces cerevisiae homologue of CHS1/beige, functions in cell wall formation and protein sorting. Traffic. 2004 Sep;5(9):700-10. PMID:15296494 doi:http://dx.doi.org/10.1111/j.1600-0854.2004.00213.x
↑ K-M Chen C, Hudock MP, Zhang Y, Guo RT, Cao R, No JH, Liang PH, Ko TP, Chang TH, Chang SC, Song Y, Axelson J, Kumar A, Wang AH, Oldfield E. Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation. J Med Chem. 2008 Sep 25;51(18):5594-607. PMID:18800762 doi:10.1021/jm800325y

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2z7i"

@@ Line 1: / Line 1: @@
 ==S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with inhibitor BPH-742==
 <StructureSection load='2z7i' size='340' side='right' caption='[[2z7i]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=742:(2,2-DIPHOSPHONOETHYL)(DODECYL)DIMETHYLPHOSPHONIUM'>742</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2z7h|2z7h]]</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=2z7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z7i OCA], [http://pdbe.org/2z7i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2z7i RCSB], [http://www.ebi.ac.uk/pdbsum/2z7i PDBsum]</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=2z7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z7i OCA], [http://pdbe.org/2z7i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2z7i RCSB], [http://www.ebi.ac.uk/pdbsum/2z7i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2z7i ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z7/2z7i_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z7/2z7i_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2z7i

From Proteopedia

Revision as of 09:07, 17 October 2018

S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with inhibitor BPH-742

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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