6oag: Difference between revisions
New page: '''Unreleased structure''' The entry 6oag is ON HOLD until Paper Publication Authors: Park, J., Berghuis, A.M. Description: Crystal structure of human FPPS in complex with an allosteri... |
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==Crystal structure of human FPPS in complex with an allosteric inhibitor YF-02-82== | |||
<StructureSection load='6oag' size='340' side='right'caption='[[6oag]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6oag]] 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=6OAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OAG FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M2Y:[(1S)-1-{[6-(3-chloro-4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]amino}-2-phenylethyl]phosphonic+acid'>M2Y</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=6oag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oag OCA], [https://pdbe.org/6oag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oag RCSB], [https://www.ebi.ac.uk/pdbsum/6oag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oag ProSAT]</span></td></tr> | |||
</table> | |||
== 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Thienopyrimidine-based allosteric inhibitors of the human farnesyl pyrophosphate synthase (hFPPS), characterized by a chiral alpha-aminophosphonic acid moiety, were synthesized as enantiomerically enriched pairs, and their binding mode was investigated by X-ray crystallography. A general consensus in the binding orientation of all (R)- and (S)-enantiomers was revealed. This finding is a prerequisite for establishing a reliable structure-activity relationship (SAR) model. | |||
Chirality-Driven Mode of Binding of alpha-Aminophosphonic Acid-Based Allosteric Inhibitors of the Human Farnesyl Pyrophosphate Synthase (hFPPS).,Feng Y, Park J, Li SG, Boutin R, Viereck P, Schilling MA, Berghuis AM, Tsantrizos YS J Med Chem. 2019 Oct 16. doi: 10.1021/acs.jmedchem.9b01104. PMID:31577901<ref>PMID:31577901</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6oag" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
==See Also== | |||
*[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Berghuis AM]] | |||
[[Category: Park J]] | |||
Latest revision as of 10:06, 11 October 2023
Crystal structure of human FPPS in complex with an allosteric inhibitor YF-02-82Crystal structure of human FPPS in complex with an allosteric inhibitor YF-02-82
Structural highlights
FunctionFPPS_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 PubMedThienopyrimidine-based allosteric inhibitors of the human farnesyl pyrophosphate synthase (hFPPS), characterized by a chiral alpha-aminophosphonic acid moiety, were synthesized as enantiomerically enriched pairs, and their binding mode was investigated by X-ray crystallography. A general consensus in the binding orientation of all (R)- and (S)-enantiomers was revealed. This finding is a prerequisite for establishing a reliable structure-activity relationship (SAR) model. Chirality-Driven Mode of Binding of alpha-Aminophosphonic Acid-Based Allosteric Inhibitors of the Human Farnesyl Pyrophosphate Synthase (hFPPS).,Feng Y, Park J, Li SG, Boutin R, Viereck P, Schilling MA, Berghuis AM, Tsantrizos YS J Med Chem. 2019 Oct 16. doi: 10.1021/acs.jmedchem.9b01104. PMID:31577901[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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