6rgk - Revision history

OCA at 12:20, 24 January 2024

OCA — Wed, 24 Jan 2024 12:20:01 GMT

←Older revision		Revision as of 12:20, 24 January 2024
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	<StructureSection load='6rgk' size='340' side='right'caption='[[6rgk]], [[Resolution\|resolution]] 2.03Å' scene=''>		<StructureSection load='6rgk' size='340' side='right'caption='[[6rgk]], [[Resolution\|resolution]] 2.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6rgk]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Trypanosoma_(trypanozoon)_brucei~~ Trypanosoma ~~(trypanozoon)~~ brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RGK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6RGK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6rgk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RGK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RGK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K3N:3-[5-[(4~{a}~{R},8~{a}~{S})-3-cycloheptyl-4-oxidanylidene-4~{a},5,6,7,8,8~{a}-hexahydrophthalazin-1-yl]-2-methoxy-phenyl]-~{N}-butyl-prop-2-ynamide'>K3N</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.03Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6gxq\|6gxq]], [[6hwo\|6hwo]], [[6rb6\|6rb6]], [[6rcw\|6rcw]], [[6rfn\|6rfn]], [[6rfw\|6rfw]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K3N:3-[5-[(4~{a}~{R},8~{a}~{S})-3-cycloheptyl-4-oxidanylidene-4~{a},5,6,7,8,8~{a}-hexahydrophthalazin-1-yl]-2-methoxy-phenyl]-~{N}-butyl-prop-2-ynamide'>K3N</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDEB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</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=6rgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rgk OCA], [https://pdbe.org/6rgk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rgk RCSB], [https://www.ebi.ac.uk/pdbsum/6rgk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rgk 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=6rgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rgk OCA], [~~http~~://pdbe.org/6rgk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6rgk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6rgk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6rgk ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q8WQX9_9TRYP Q8WQX9_9TRYP]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6rgk" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6rgk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Brown, D G~~]]	+	[[Category: Trypanosoma brucei]]
-	[[Category: ~~Singh, A K~~]]	+	[[Category: Brown DG]]
-	[[Category: ~~African trypanosomiasis]]~~	+	[[Category: Singh AK]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Parasitic phosphodiesterase]]~~	+
-	~~[[Category: Sleeping sickness~~]]	+

OCA at 17:33, 14 August 2019

OCA — Wed, 14 Aug 2019 17:33:39 GMT

←Older revision		Revision as of 17:33, 14 August 2019
Line 3:		Line 3:
	<StructureSection load='6rgk' size='340' side='right'caption='[[6rgk]], [[Resolution\|resolution]] 2.03Å' scene=''>		<StructureSection load='6rgk' size='340' side='right'caption='[[6rgk]], [[Resolution\|resolution]] 2.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6rgk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RGK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RGK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6rgk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RGK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RGK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K3N:3-[5-[(4~{a}~{R},8~{a}~{S})-3-cycloheptyl-4-oxidanylidene-4~{a},5,6,7,8,8~{a}-hexahydrophthalazin-1-yl]-2-methoxy-phenyl]-~{N}-butyl-prop-2-ynamide'>K3N</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K3N:3-[5-[(4~{a}~{R},8~{a}~{S})-3-cycloheptyl-4-oxidanylidene-4~{a},5,6,7,8,8~{a}-hexahydrophthalazin-1-yl]-2-methoxy-phenyl]-~{N}-butyl-prop-2-ynamide'>K3N</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6gxq\|6gxq]], [[6hwo\|6hwo]], [[6rb6\|6rb6]], [[6rcw\|6rcw]], [[6rfn\|6rfn]], [[6rfw\|6rfw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6gxq\|6gxq]], [[6hwo\|6hwo]], [[6rb6\|6rb6]], [[6rcw\|6rcw]], [[6rfn\|6rfn]], [[6rfw\|6rfw]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDEB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</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=6rgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rgk OCA], [http://pdbe.org/6rgk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rgk RCSB], [http://www.ebi.ac.uk/pdbsum/6rgk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rgk 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=6rgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rgk OCA], [http://pdbe.org/6rgk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rgk RCSB], [http://www.ebi.ac.uk/pdbsum/6rgk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rgk ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibitors against Trypanosoma brucei phosphodiesterase B1 (TbrPDEB1) and B2 (TbrPDEB2) have gained interest as new treatments for human African trypanosomiasis. The recently reported alkynamide tetrahydrophthalazinones, which show submicromolar activities against TbrPDEB1 and anti-T. brucei activity, have been used as starting point for the discovery of new TbrPDEB1 inhibitors. Structure-based design indicated that the alkynamide-nitrogen atom can be readily decorated, leading to the discovery of 37, a potent TbrPDEB1 inhibitor with submicromolar activities against T. brucei parasites. Furthermore, 37 is more potent against TbrPDEB1 than hPDE4 and shows no cytotoxicity on human MRC-5 cells. The crystal structures of the catalytic domain of TbrPDEB1 co-crystalized with several different alkynamides show a bidentate interaction with key-residue Gln874, but no interaction with the parasite-specific P-pocket, despite being (uniquely) a more potent inhibitor for the parasite PDE. Incubation of blood stream form trypanosomes by 37 increases intracellular cAMP levels and results in the distortion of the cell cycle and cell death, validating phosphodiesterase inhibition as mode of action.
		+
		+	Alkynamide phthalazinones as a new class of TbrPDEB1 inhibitors (Part 2).,de Heuvel E, Singh AK, Boronat P, Kooistra AJ, van der Meer T, Sadek P, Blaazer AR, Shaner NC, Bindels DS, Caljon G, Maes L, Sterk GJ, Siderius M, Oberholzer M, de Esch IJP, Brown DG, Leurs R Bioorg Med Chem. 2019 Jul 5. pii: S0968-0896(19)30790-4. doi:, 10.1016/j.bmc.2019.06.026. PMID:31378593<ref>PMID:31378593</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6rgk" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:28, 24 July 2019

OCA — Wed, 24 Jul 2019 06:28:37 GMT

←Older revision		Revision as of 06:28, 24 July 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6rgk is ON HOLD until Paper Publication~~	+	==Crystal structure of T. brucei PDE-B1 catalytic domain with inhibitor NPD-055==
-		+	<StructureSection load='6rgk' size='340' side='right'caption='[[6rgk]], [[Resolution\|resolution]] 2.03Å' scene=''>
-	~~Authors: Singh, A.K., Brown, D.G.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6rgk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RGK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RGK FirstGlance]. <br>
-	~~Description:~~ Crystal structure of T. brucei PDE-B1 catalytic domain with inhibitor NPD-055	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K3N:3-[5-[(4~{a}~{R},8~{a}~{S})-3-cycloheptyl-4-oxidanylidene-4~{a},5,6,7,8,8~{a}-hexahydrophthalazin-1-yl]-2-methoxy-phenyl]-~{N}-butyl-prop-2-ynamide'>K3N</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6gxq\|6gxq]], [[6hwo\|6hwo]], [[6rb6\|6rb6]], [[6rcw\|6rcw]], [[6rfn\|6rfn]], [[6rfw\|6rfw]]</td></tr>
-	[[Category: Brown, D.G]]	+	<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=6rgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rgk OCA], [http://pdbe.org/6rgk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rgk RCSB], [http://www.ebi.ac.uk/pdbsum/6rgk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rgk ProSAT]</span></td></tr>
-	[[Category: Singh, A.K]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Brown, D G]]
		+	[[Category: Singh, A K]]
		+	[[Category: African trypanosomiasis]]
		+	[[Category: Hydrolase]]
		+	[[Category: Parasitic phosphodiesterase]]
		+	[[Category: Sleeping sickness]]

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

OCA — Wed, 24 Apr 2019 05:17:55 GMT

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

←Older revision

Revision as of 05:17, 24 April 2019

OCA: New page: '''Unreleased structure''' The entry 6rgk is ON HOLD until Paper Publication Authors: Singh, A.K., Brown, D.G. Description: Crystal structure of T. brucei PDE-B1 catalytic domain with ...

OCA — Wed, 24 Apr 2019 05:17:53 GMT

New page: '''Unreleased structure''' The entry 6rgk is ON HOLD until Paper Publication Authors: Singh, A.K., Brown, D.G. Description: Crystal structure of T. brucei PDE-B1 catalytic domain with ...

New page

'''Unreleased structure'''

The entry 6rgk is ON HOLD until Paper Publication

Authors: Singh, A.K., Brown, D.G.

Description: Crystal structure of T. brucei PDE-B1 catalytic domain with inhibitor NPD-055
[[Category: Unreleased Structures]]
[[Category: Brown, D.G]]
[[Category: Singh, A.K]]