4rxa: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4rxa]] 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=4RXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RXA FirstGlance]. <br>
<table><tr><td colspan='2'>[[4rxa]] 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=4RXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RXA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3F2:N,N-BIS[3-(4,5-DIHYDRO-1H-IMIDAZOL-2-YL)PHENYL]BIPHENYL-4,4-DICARBOXAMIDE'>3F2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3F2:N,N-BIS[3-(4,5-DIHYDRO-1H-IMIDAZOL-2-YL)PHENYL]BIPHENYL-4,4-DICARBOXAMIDE'>3F2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4rxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rxa OCA], [https://pdbe.org/4rxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rxa RCSB], [https://www.ebi.ac.uk/pdbsum/4rxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rxa 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=4rxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rxa OCA], [https://pdbe.org/4rxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rxa RCSB], [https://www.ebi.ac.uk/pdbsum/4rxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rxa 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 ==
Farnesyl diphosphate synthase (FPPS) is an important drug target for bone resorption, cancer, and some infectious diseases. Here, we report five new structures including two having unique bound ligand geometries. The diamidine inhibitor 7 binds to human FPPS close to the homoallylic (S2) and allosteric (S3) sites and extends into a new site, here called S4. With the bisphosphonate inhibitor 8, two molecules bind to Trypanosoma brucei FPPS, one molecule in the allylic site (S1) and the other close to S2, the first observation of two bisphosphonate molecules bound to FPPS. We also report the structures of apo-FPPS from T. brucei, together with two more bisphosphonate-bound structures (2,9), for purposes of comparison. The diamidine structure is of particular interest because 7 could represent a new lead for lipophilic FPPS inhibitors, while 8 has low micromolar activity against T. brucei, the causative agent of human African trypanosomiasis.
Farnesyl diphosphate synthase inhibitors with unique ligand-binding geometries.,Liu YL, Cao R, Wang Y, Oldfield E ACS Med Chem Lett. 2015 Jan 29;6(3):349-54. doi: 10.1021/ml500528x. eCollection, 2015 Mar 12. PMID:25815158<ref>PMID:25815158</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4rxa" 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/>
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</StructureSection>
</StructureSection>

Latest revision as of 12:56, 1 March 2024

Crystal structure of human farnesyl diphosphate synthase in complex with BPH-1358

4rxa, resolution 2.20Å

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