6r4v - Revision history

OCA at 12:15, 24 January 2024

OCA — Wed, 24 Jan 2024 12:15:11 GMT

←Older revision		Revision as of 12:15, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6r4v' size='340' side='right'caption='[[6r4v]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='6r4v' size='340' side='right'caption='[[6r4v]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6r4v]] is a 6 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=6R4V OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6R4V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6r4v]] is a 6 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=6R4V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R4V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BFQ:IBANDRONATE'>BFQ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.202Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GGPS1 ([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=BFQ:IBANDRONATE'>BFQ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6r4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r4v OCA], [~~http~~://pdbe.org/6r4v PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6r4v RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6r4v PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6r4v 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=6r4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r4v OCA], [https://pdbe.org/6r4v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r4v RCSB], [https://www.ebi.ac.uk/pdbsum/6r4v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r4v ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GGPPS_HUMAN GGPPS_HUMAN]] Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.	+	[https://www.uniprot.org/uniprot/GGPPS_HUMAN GGPPS_HUMAN] Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.
	<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 6r4v" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6r4v" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Geranylgeranyl pyrophosphate synthase 3D structures\|Geranylgeranyl pyrophosphate synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Giladi, M]]	+	[[Category: Giladi M]]
-	[[Category: Haitin, Y]]	+	[[Category: Haitin Y]]
-	[[Category: Lisnyansky, M]]	+	[[Category: Lisnyansky M]]
-	~~[[Category: Bisphosphonate]]~~	+
-	~~[[Category: Geranylgeranyl diphosphate]]~~	+
-	~~[[Category: Ibandronate]]~~	+
-	~~[[Category: Prenyltransferase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:23, 10 October 2019

OCA — Thu, 10 Oct 2019 06:23:32 GMT

←Older revision		Revision as of 06:23, 10 October 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6r4v is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of human geranylgeranyl diphosphate synthase bound to ibandronate==
		+	<StructureSection load='6r4v' size='340' side='right'caption='[[6r4v]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6r4v]] is a 6 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=6R4V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R4V FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BFQ:IBANDRONATE'>BFQ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GGPS1 ([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=6r4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r4v OCA], [http://pdbe.org/6r4v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r4v RCSB], [http://www.ebi.ac.uk/pdbsum/6r4v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r4v ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GGPPS_HUMAN GGPPS_HUMAN]] Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Geranylgeranyl diphosphate synthase (GGPPS) is a central metalloenzyme in the mevalonate pathway, crucial for the prenylation of small GTPases. As small GTPases are pivotal for cellular survival, GGPPS was highlighted as a potential target for treating human diseases, including solid and hematologic malignancies and parasitic infections. Most available GGPPS inhibitors are bisphosphonates, but the clinically available compounds demonstrate poor pharmacokinetic properties. Although the design of novel bisphosphonates with improved physicochemical properties is highly desirable, the structure of wild-type human GGPPS (hGGPPS) bound to a bisphosphonate has not been resolved. Moreover, various metal-bisphosphonate-binding stoichiometries were previously reported in structures of yeast GGPPS (yGGPPS), hampering computational drug design with metal-binding pharmacophores (MBP). In this study, we report the 2.2 A crystal structure of hGGPPS in complex with ibandronate, clearly depicting the involvement of three Mg(2+) ions in bisphosphonate-protein interactions. Using drug-binding assays and computational docking, we show that the assignment of three Mg(2+) ions to the binding site of both hGGPPS and yGGPPS greatly improves the correlation between calculated binding energies and experimentally measured affinities. This work provides a structural basis for future rational design of additional MBP-harboring drugs targeting hGGPPS. SIGNIFICANCE STATEMENT: Bisphosphonates are inhibitors of geranylgeranyl diphosphate synthase (GGPPS), a metalloenzyme crucial for cell survival. Bisphosphonate binding depends on coordination by Mg(2+) ions, but various Mg(2+)-bisphosphonate-binding stoichiometries were previously reported. In this study, we show that three Mg(2+) ions are vital for drug binding and provide a structural basis for future computational design of GGPPS inhibitors.

-	~~Authors~~:	+	Metal Coordination Is Crucial for Geranylgeranyl Diphosphate Synthase-Bisphosphonate Interactions: A Crystallographic and Computational Analysis.,Lisnyansky M, Yariv E, Segal O, Marom M, Loewenstein A, Ben-Tal N, Giladi M, Haitin Y Mol Pharmacol. 2019 Nov;96(5):580-588. doi: 10.1124/mol.119.117499. Epub 2019 Aug, 19. PMID:31427399<ref>PMID:31427399</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6r4v" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Giladi, M]]
		+	[[Category: Haitin, Y]]
		+	[[Category: Lisnyansky, M]]
		+	[[Category: Bisphosphonate]]
		+	[[Category: Geranylgeranyl diphosphate]]
		+	[[Category: Ibandronate]]
		+	[[Category: Prenyltransferase]]
		+	[[Category: Transferase]]

OCA: Protected "6r4v" [edit=sysop:move=sysop]

OCA — Wed, 03 Apr 2019 04:57:09 GMT

Protected "6r4v" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:57, 3 April 2019

OCA: New page: '''Unreleased structure''' The entry 6r4v is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 03 Apr 2019 04:57:07 GMT

New page: '''Unreleased structure''' The entry 6r4v is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6r4v is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]