5ksx - Revision history

OCA at 10:53, 27 September 2023

OCA — Wed, 27 Sep 2023 10:53:27 GMT

←Older revision		Revision as of 10:53, 27 September 2023
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	==Crystal structure of human FPPS in complex with an allosteric inhibitor AM-02-072==		==Crystal structure of human FPPS in complex with an allosteric inhibitor AM-02-072==
-	<StructureSection load='5ksx' size='340' side='right' caption='[[5ksx]], [[Resolution\|resolution]] 2.65Å' scene=''>	+	<StructureSection load='5ksx' size='340' side='right'caption='[[5ksx]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ksx]] 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=5KSX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5KSX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ksx]] 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=5KSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KSX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7AM:[[(2~{S})-2-[[6-(4-METHYLPHENYL)THIENO[2,3-D]PYRIMIDIN-4-YL]AMINO]-3-PHENYL-PROPANOYL]AMINO]PHOSPHONIC+ACID'>7AM</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]] 2.65Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7AM:[[(2~{S})-2-[[6-(4-METHYLPHENYL)THIENO[2,3-D]PYRIMIDIN-4-YL]AMINO]-3-PHENYL-PROPANOYL]AMINO]PHOSPHONIC+ACID'>7AM</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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ksx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ksx OCA], [~~http~~://pdbe.org/5ksx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ksx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ksx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ksx 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=5ksx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ksx OCA], [https://pdbe.org/5ksx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ksx RCSB], [https://www.ebi.ac.uk/pdbsum/5ksx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ksx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5ksx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ksx" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Farnesyl diphosphate synthase 3D structures\|Farnesyl diphosphate synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Berghuis, A M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Matralis, A~~]]	+	[[Category: Berghuis AM]]
-	[[Category: ~~Park, J~~]]	+	[[Category: Matralis A]]
-	[[Category: ~~Tsantrizos, Y S~~]]	+	[[Category: Park J]]
-	[[Category: ~~Transferase-transferase inhibitor complex~~]]	+	[[Category: Tsantrizos YS]]

OCA at 13:03, 6 November 2017

OCA — Mon, 06 Nov 2017 13:03:06 GMT

←Older revision		Revision as of 13:03, 6 November 2017
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	<StructureSection load='5ksx' size='340' side='right' caption='[[5ksx]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='5ksx' size='340' side='right' caption='[[5ksx]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ksx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KSX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ksx]] 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=5KSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KSX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7AM:[[(2~{S})-2-[[6-(4-METHYLPHENYL)THIENO[2,3-D]PYRIMIDIN-4-YL]AMINO]-3-PHENYL-PROPANOYL]AMINO]PHOSPHONIC+ACID'>7AM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7AM:[[(2~{S})-2-[[6-(4-METHYLPHENYL)THIENO[2,3-D]PYRIMIDIN-4-YL]AMINO]-3-PHENYL-PROPANOYL]AMINO]PHOSPHONIC+ACID'>7AM</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 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=5ksx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ksx OCA], [http://pdbe.org/5ksx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ksx RCSB], [http://www.ebi.ac.uk/pdbsum/5ksx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ksx ProSAT]</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=5ksx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ksx OCA], [http://pdbe.org/5ksx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ksx RCSB], [http://www.ebi.ac.uk/pdbsum/5ksx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ksx ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Berghuis, A M]]		[[Category: Berghuis, A M]]
	[[Category: Matralis, A]]		[[Category: Matralis, A]]

OCA at 21:08, 15 March 2017

OCA — Wed, 15 Mar 2017 21:08:31 GMT

←Older revision		Revision as of 21:08, 15 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ksx is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of human FPPS in complex with an allosteric inhibitor AM-02-072==
		+	<StructureSection load='5ksx' size='340' side='right' caption='[[5ksx]], [[Resolution\|resolution]] 2.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ksx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KSX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7AM:[[(2~{S})-2-[[6-(4-METHYLPHENYL)THIENO[2,3-D]PYRIMIDIN-4-YL]AMINO]-3-PHENYL-PROPANOYL]AMINO]PHOSPHONIC+ACID'>7AM</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ksx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ksx OCA], [http://pdbe.org/5ksx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ksx RCSB], [http://www.ebi.ac.uk/pdbsum/5ksx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ksx ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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 ==
		+	The human farnesyl pyrophosphate synthase (hFPPS), a key regulatory enzyme in the mevalonate pathway, catalyzes the biosynthesis of the C-15 isoprenoid farnesyl pyrophosphate (FPP). FPP plays a crucial role in the post-translational prenylation of small GTPases that perform a plethora of cellular functions. Although hFPPS is a well-established therapeutic target for lytic bone diseases, the currently available bisphosphonate drugs exhibit poor cellular uptake and distribution into nonskeletal tissues. Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating nonskeletal diseases. Hit-to-lead optimization of a new series of thienopyrimidine-based monosphosphonates (ThP-MPs) led to the identification of analogs with nanomolar potency in inhibiting hFPPS. Their interactions with the allosteric pocket of the enzyme were characterized by crystallography, and the results provide further insight into the pharmacophore requirements for allosteric inhibition.

-	~~Authors~~:	+	Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase.,Park J, Leung CY, Matralis AN, Lacbay CM, Tsakos M, Fernandez De Troconiz G, Berghuis AM, Tsantrizos YS J Med Chem. 2017 Mar 9;60(5):2119-2134. doi: 10.1021/acs.jmedchem.6b01888. Epub, 2017 Feb 28. PMID:28208018<ref>PMID:28208018</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5ksx" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Berghuis, A M]]
		+	[[Category: Matralis, A]]
		+	[[Category: Park, J]]
		+	[[Category: Tsantrizos, Y S]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 02:01, 4 August 2016

OCA — Thu, 04 Aug 2016 02:01:22 GMT

←Older revision		Revision as of 02:01, 4 August 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5ksx is ON HOLD	+	The entry 5ksx is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "5ksx" [edit=sysop:move=sysop]

OCA — Tue, 26 Jul 2016 12:50:33 GMT

Protected "5ksx" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:50, 26 July 2016

OCA: New page: '''Unreleased structure''' The entry 5ksx is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Tue, 26 Jul 2016 12:50:32 GMT

New page: '''Unreleased structure''' The entry 5ksx is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5ksx is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]