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4ga3

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Revision as of 11:57, 4 August 2016

Crystal Structure of Human Farnesyl Diphosphate Synthase in Complex with BPH-1260

Structural highlights

4ga3 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	FDPS, FPS, KIAA1293 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

Publication Abstract from PubMed

We synthesized 30 lipophilic bisphosphonates and tested them in malaria parasite killing (targeting parasite geranylgeranyl diphosphate synthase, GGPPS) as well in human gammadelta T cell activation (targeting human farnesyl diphosphate synthase, FPPS). Similar patterns of activity were seen in inhibiting human FPPS and Plasmodium GGPPS, with short to medium chain-length species having most activity. In cells, shorter chain-length species had low activity, due to poor membrane permeability, and longer chain length species were poor enzyme inhibitors. Optimal activity was thus seen with ~C10 side-chains, which have the best combination of enzyme inhibition and cell penetration. We also solved the crystal structure of one potent inhibitor, bound to FPPS. The results are of interest since they suggest the possibility of a combined chemo/immuno-therapeutic approach to anti-malarial development in which both direct parasite killing as well as gammadelta T cell activation can be achieved with a single compound.

Chemo-Immunotherapeutic Anti-Malarials Targeting Isoprenoid Biosynthesis.,Zhang Y, Zhu W, Liu YL, Wang H, Wang K, Li K, No JH, Ayong L, Gulati A, Pang R, Freitas-Junior L, Morita CT, Old-Field E ACS Med Chem Lett. 2013 Apr 11;4(4):423-427. PMID:23610597^[1]

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

References

↑ Zhang Y, Zhu W, Liu YL, Wang H, Wang K, Li K, No JH, Ayong L, Gulati A, Pang R, Freitas-Junior L, Morita CT, Old-Field E. Chemo-Immunotherapeutic Anti-Malarials Targeting Isoprenoid Biosynthesis. ACS Med Chem Lett. 2013 Apr 11;4(4):423-427. PMID:23610597 doi:http://dx.doi.org/10.1021/ml4000436

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ga3"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human Farnesyl Diphosphate Synthase in Complex with BPH-1260==
 <StructureSection load='4ga3' size='340' side='right' caption='[[4ga3]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ga3]] 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=4GA3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GA3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ga3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GA3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GA3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4GA:1-BUTYL-3-(2-HYDROXY-2,2-DIPHOSPHONOETHYL)-1H-IMIDAZOL-3-IUM'>4GA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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='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 HUMAN])</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=4ga3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ga3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ga3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ga3 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=4ga3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ga3 OCA], [http://pdbe.org/4ga3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ga3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ga3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ga3 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ga3" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Liu, Y L]]
 [[Category: Oldfield, E]]

4ga3

From Proteopedia

Revision as of 11:57, 4 August 2016

Crystal Structure of Human Farnesyl Diphosphate Synthase in Complex with BPH-1260

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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