6m89 - Revision history

OCA at 06:26, 11 October 2023

2023-10-11T06:26:08Z

←Older revision		Revision as of 06:26, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6m89' size='340' side='right'caption='[[6m89]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='6m89' size='340' side='right'caption='[[6m89]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6m89]] 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=6M89 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6M89 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6m89]] 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=6M89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M89 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=QUE:3~~,~~5,7,3,4-PENTAHYDROXYFLAVONE'>QUE</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]] 1.85Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~IPMK, IMPK ([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=QUE:3,5,7,3,4-PENTAHYDROXYFLAVONE'>QUE</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=6m89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m89 OCA], [~~http~~://pdbe.org/6m89 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6m89 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6m89 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6m89 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=6m89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m89 OCA], [https://pdbe.org/6m89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m89 RCSB], [https://www.ebi.ac.uk/pdbsum/6m89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m89 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/IPMK_HUMAN IPMK_HUMAN]] Inositol phosphate kinase with a broad substrate specificity. Has a preference for inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4).<ref>PMID:12027805</ref> <ref>PMID:12223481</ref>	+	[https://www.uniprot.org/uniprot/IPMK_HUMAN IPMK_HUMAN] Inositol phosphate kinase with a broad substrate specificity. Has a preference for inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4).<ref>PMID:12027805</ref> <ref>PMID:12223481</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Shears~~, S B~~]]	+	[[Category: Shears SB]]
-	[[Category: Wang, H]]	+	[[Category: Wang H]]
-	~~[[Category: Flavonoid]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Inositol]]~~	+
-	~~[[Category: Inositol polyphosphate]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Natural product]]~~	+
-	~~[[Category: Quercetin]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 09:17, 1 May 2019

2019-05-01T09:17:54Z

←Older revision		Revision as of 09:17, 1 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6m89 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the core catalytic domain of human inositol phosphate multikinase in complex with quercetin==
		+	<StructureSection load='6m89' size='340' side='right'caption='[[6m89]], [[Resolution\|resolution]] 1.85Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6m89]] 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=6M89 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6M89 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QUE:3,5,7,3,4-PENTAHYDROXYFLAVONE'>QUE</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IPMK, IMPK ([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=6m89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m89 OCA], [http://pdbe.org/6m89 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m89 RCSB], [http://www.ebi.ac.uk/pdbsum/6m89 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m89 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/IPMK_HUMAN IPMK_HUMAN]] Inositol phosphate kinase with a broad substrate specificity. Has a preference for inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4).<ref>PMID:12027805</ref> <ref>PMID:12223481</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Dietary flavonoids inhibit certain protein kinases and phospholipid kinases by competing for their ATP-binding sites. These nucleotide pockets have structural elements that are well-conserved in two human small-molecule kinases, inositol hexakisphosphate kinase (IP6K) and inositol polyphosphate multikinase (IPMK), which synthesize multifunctional inositol phosphate cell signals. Herein, we demonstrate that both kinases are inhibited by quercetin and 16 related flavonoids; IP6K is the preferred target. Relative inhibitory activities were rationalized by X-ray analysis of kinase/flavonoid crystal structures; this detailed structure-activity analysis revealed hydrophobic and polar ligand/protein interactions, the degree of flexibility of key amino acid side chains, and the importance of water molecules. The seven most potent IP6K inhibitors were incubated with intact HCT116 cells at concentrations of 2.5 muM; diosmetin was the most selective and effective IP6K inhibitor (>70% reduction in activity). Our data can instruct on pharmacophore properties to assist the future development of inositol phosphate kinase inhibitors. Finally, we propose that dietary flavonoids may inhibit IP6K activity in cells that line the gastrointestinal tract.

-	~~Authors~~: ~~Wang, H~~., Shears, S.B.	+	Inhibition of Inositol Polyphosphate Kinases by Quercetin and Related Flavonoids: A Structure-Activity Analysis.,Gu C, Stashko MA, Puhl-Rubio AC, Chakraborty M, Chakraborty A, Frye SV, Pearce KH, Wang X, Shears SB, Wang H J Med Chem. 2019 Feb 14;62(3):1443-1454. doi: 10.1021/acs.jmedchem.8b01593. Epub , 2019 Jan 25. PMID:30624931<ref>PMID:30624931</ref>

-	~~Description: Crystal structure~~ of the ~~core catalytic domain~~ of ~~human inositol phosphate multikinase in complex with quercetin~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Shears, S.B]]	+	<div class="pdbe-citations 6m89" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Shears, S B]]
	[[Category: Wang, H]]		[[Category: Wang, H]]
		+	[[Category: Flavonoid]]
		+	[[Category: Inhibitor]]
		+	[[Category: Inositol]]
		+	[[Category: Inositol polyphosphate]]
		+	[[Category: Kinase]]
		+	[[Category: Natural product]]
		+	[[Category: Quercetin]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "6m89" [edit=sysop:move=sysop]

2018-08-29T06:06:14Z

Protected "6m89" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:06, 29 August 2018

OCA: New page: '''Unreleased structure''' The entry 6m89 is ON HOLD until Paper Publication Authors: Wang, H., Shears, S.B. Description: Crystal structure of the core catalytic domain of human inosit...

2018-08-29T06:06:13Z

New page: '''Unreleased structure''' The entry 6m89 is ON HOLD until Paper Publication Authors: Wang, H., Shears, S.B. Description: Crystal structure of the core catalytic domain of human inosit...

New page

'''Unreleased structure'''

The entry 6m89 is ON HOLD until Paper Publication

Authors: Wang, H., Shears, S.B.

Description: Crystal structure of the core catalytic domain of human inositol phosphate multikinase in complex with quercetin
[[Category: Unreleased Structures]]
[[Category: Shears, S.B]]
[[Category: Wang, H]]