4dem

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:33, 14 March 2024) (edit) (undo)
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4dem]] 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=4DEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DEM FirstGlance]. <br>
<table><tr><td colspan='2'>[[4dem]] 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=4DEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DEM FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=YS4:[({4-[4-(PROPAN-2-YLOXY)PHENYL]PYRIDIN-2-YL}AMINO)METHANEDIYL]BIS(PHOSPHONIC+ACID)'>YS4</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]] 1.85&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=YS4:[({4-[4-(PROPAN-2-YLOXY)PHENYL]PYRIDIN-2-YL}AMINO)METHANEDIYL]BIS(PHOSPHONIC+ACID)'>YS4</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=4dem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dem OCA], [https://pdbe.org/4dem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dem RCSB], [https://www.ebi.ac.uk/pdbsum/4dem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dem ProSAT]</span></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=4dem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dem OCA], [https://pdbe.org/4dem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dem RCSB], [https://www.ebi.ac.uk/pdbsum/4dem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dem ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
-
[[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.
+
[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.
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
Human farnesyl pyrophosphate synthase (hFPPS) controls intracellular levels of FPP and post-translational prenylation of small GTPase proteins, which are essential for cell signaling and cell proliferation. Clinical investigations provide evidence that N-BP inhibitors of hFPPS are disease modifying agents that improve survival of multiple myeloma (MM) patients via mechanisms unrelated to their skeletal effects. A new series of N-BPs was designed that interact with a larger portion of the GPP subpocket, as compared to the current therapeutic drugs, and rigidify the (364)KRRK(367) tail of hFPPS in the closed conformation in the absence of IPP. An analogue of this series was used to demonstrate inhibition of the intended biological target, resulting in apoptosis and down-regulation of ERK phosphorylation in human MM cell lines.
+
-
 
+
-
Design and Synthesis of Active Site Inhibitors of the Human Farnesyl Pyrophosphate Synthase: Apoptosis and Inhibition of ERK Phosphorylation in Multiple Myeloma Cells.,Lin YS, Park J, De Schutter JW, Huang XF, Berghuis AM, Sebag M, Tsantrizos YS J Med Chem. 2012 Mar 19. PMID:22390415<ref>PMID:22390415</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 4dem" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==
*[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]]
*[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]]
-
== References ==
 
-
<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Current revision

Crystal structure of human FPPS in complex with YS_04_70

PDB ID 4dem

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dem"
Personal tools