5b4k - Revision history

OCA at 15:59, 8 November 2023

OCA — Wed, 08 Nov 2023 15:59:47 GMT

←Older revision		Revision as of 15:59, 8 November 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5b4k]] is a 2 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=5B4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B4K FirstGlance]. <br>		<table><tr><td colspan='2'>[[5b4k]] is a 2 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=5B4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B4K FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DT:N-(4-((5-METHYL-5H-PYRROLO[3,2-D]PYRIMIDIN-4-YL)OXY)PHENYL)-1H-BENZIMIDAZOL-2-AMINE'>6DT</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]] 2.9Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DT:N-(4-((5-METHYL-5H-PYRROLO[3,2-D]PYRIMIDIN-4-YL)OXY)PHENYL)-1H-BENZIMIDAZOL-2-AMINE'>6DT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5b4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b4k OCA], [https://pdbe.org/5b4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b4k RCSB], [https://www.ebi.ac.uk/pdbsum/5b4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b4k 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=5b4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b4k OCA], [https://pdbe.org/5b4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b4k RCSB], [https://www.ebi.ac.uk/pdbsum/5b4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b4k ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:38, 31 May 2023

OCA — Wed, 31 May 2023 06:38:33 GMT

←Older revision		Revision as of 06:38, 31 May 2023
Line 3:		Line 3:
	<StructureSection load='5b4k' size='340' side='right'caption='[[5b4k]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='5b4k' size='340' side='right'caption='[[5b4k]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5b4k]] is a 2 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=5B4K OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5B4K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5b4k]] is a 2 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=5B4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B4K FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6DT:N-(4-((5-METHYL-5H-PYRROLO[3,2-D]PYRIMIDIN-4-YL)OXY)PHENYL)-1H-BENZIMIDAZOL-2-AMINE'>6DT</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" id="ligandDat"><scene name='pdbligand=6DT:N-(4-((5-METHYL-5H-PYRROLO[3,2-D]PYRIMIDIN-4-YL)OXY)PHENYL)-1H-BENZIMIDAZOL-2-AMINE'>6DT</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">[[5b4l\|5b4l]]</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=5b4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b4k OCA], [https://pdbe.org/5b4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b4k RCSB], [https://www.ebi.ac.uk/pdbsum/5b4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b4k ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE10A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </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=5b4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b4k OCA], [~~http~~://pdbe.org/5b4k PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5b4k RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5b4k PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5b4k ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN]] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>	+	[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~3',5'-cyclic-nucleotide phosphodiesterase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Oki, H]]	+	[[Category: Oki H]]
-	[[Category: Zama, Y]]	+	[[Category: Zama Y]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 08:46, 11 March 2020

OCA — Wed, 11 Mar 2020 08:46:09 GMT

←Older revision		Revision as of 08:46, 11 March 2020
Line 1:		Line 1:

	==Crystal structure of the catalytic domain of human PDE10A complexed with N-(4-((5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)oxy)phenyl)-1H-benzimidazol-2-amine==		==Crystal structure of the catalytic domain of human PDE10A complexed with N-(4-((5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)oxy)phenyl)-1H-benzimidazol-2-amine==
-	<StructureSection load='5b4k' size='340' side='right' caption='[[5b4k]], [[Resolution\|resolution]] 2.90Å' scene=''>	+	<StructureSection load='5b4k' size='340' side='right'caption='[[5b4k]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5b4k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B4K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5b4k]] is a 2 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=5B4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B4K FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6DT:N-(4-((5-METHYL-5H-PYRROLO[3,2-D]PYRIMIDIN-4-YL)OXY)PHENYL)-1H-BENZIMIDAZOL-2-AMINE'>6DT</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=6DT:N-(4-((5-METHYL-5H-PYRROLO[3,2-D]PYRIMIDIN-4-YL)OXY)PHENYL)-1H-BENZIMIDAZOL-2-AMINE'>6DT</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">[[5b4l\|5b4l]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5b4l\|5b4l]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE10A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </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=5b4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b4k OCA], [http://pdbe.org/5b4k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b4k RCSB], [http://www.ebi.ac.uk/pdbsum/5b4k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b4k 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=5b4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b4k OCA], [http://pdbe.org/5b4k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b4k RCSB], [http://www.ebi.ac.uk/pdbsum/5b4k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b4k ProSAT]</span></td></tr>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5b4k" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5b4k" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]		[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Oki, H]]		[[Category: Oki, H]]
	[[Category: Zama, Y]]		[[Category: Zama, Y]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 10:17, 13 July 2016

OCA — Wed, 13 Jul 2016 10:17:17 GMT

←Older revision		Revision as of 10:17, 13 July 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5b4k is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the catalytic domain of human PDE10A complexed with N-(4-((5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)oxy)phenyl)-1H-benzimidazol-2-amine==
		+	<StructureSection load='5b4k' size='340' side='right' caption='[[5b4k]], [[Resolution\|resolution]] 2.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5b4k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B4K FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6DT:N-(4-((5-METHYL-5H-PYRROLO[3,2-D]PYRIMIDIN-4-YL)OXY)PHENYL)-1H-BENZIMIDAZOL-2-AMINE'>6DT</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">[[5b4l\|5b4l]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </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=5b4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b4k OCA], [http://pdbe.org/5b4k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b4k RCSB], [http://www.ebi.ac.uk/pdbsum/5b4k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b4k ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN]] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Utilizing structure-based drug design techniques, we designed and synthesized phosphodiesterase 10A (PDE10A) inhibitors based on pyridazin-4(1H)-one. These compounds can interact with Tyr683 in the PDE10A selectivity pocket. Pyridazin-4(1H)-one derivative 1 was linked with a benzimidazole group through an alkyl spacer to interact with the OH of Tyr683 and fill the PDE10A selectivity pocket. After optimizing the linker length, we identified 1-(cyclopropylmethyl)-5-[3-(1-methyl-1H-benzimidazol-2-yl)propoxy]-3-(1-phenyl-1H -pyrazol-5-yl)pyridazin-4(1H)-one (16f) as having highly potent PDE10A inhibitory activity (IC50=0.76nM) and perfect selectivity against other PDEs (>13,000-fold, IC50=>10,000nM). The crystal structure of 16f bound to PDE10A revealed that the benzimidazole moiety was located deep within the PDE10A selectivity pocket and interacted with Tyr683. Additionally, a bidentate interaction existed between the 5-alkoxypyridazin-4(1H)-one moiety and the conserved Gln716 present in all PDEs.

-	~~Authors~~:	+	Design and synthesis of potent and selective pyridazin-4(1H)-one-based PDE10A inhibitors interacting with Tyr683 in the PDE10A selectivity pocket.,Yoshikawa M, Hitaka T, Hasui T, Fushimi M, Kunitomo J, Kokubo H, Oki H, Nakashima K, Taniguchi T Bioorg Med Chem. 2016 May 25. pii: S0968-0896(16)30382-0. doi:, 10.1016/j.bmc.2016.05.049. PMID:27301679<ref>PMID:27301679</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5b4k" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
		+	[[Category: Oki, H]]
		+	[[Category: Zama, Y]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 11:08, 15 May 2016

OCA — Sun, 15 May 2016 11:08:39 GMT

←Older revision		Revision as of 11:08, 15 May 2016
Line 3:		Line 3:
	The entry 5b4k is ON HOLD until Paper Publication		The entry 5b4k is ON HOLD until Paper Publication

-	Authors: ~~Oki, H., Zama, Y.~~	+	Authors:

	Description:		Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Zama, Y]]
-	[[Category: Oki, H]]

OCA: Protected "5b4k" [edit=sysop:move=sysop]

OCA — Tue, 10 May 2016 20:58:24 GMT

Protected "5b4k" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:58, 10 May 2016

OCA: New page: '''Unreleased structure''' The entry 5b4k is ON HOLD until Paper Publication Authors: Oki, H., Zama, Y. Description: Category: Unreleased Structures Category: Zama, Y [[Catego...

OCA — Tue, 10 May 2016 20:58:23 GMT

New page: '''Unreleased structure''' The entry 5b4k is ON HOLD until Paper Publication Authors: Oki, H., Zama, Y. Description: Category: Unreleased Structures Category: Zama, Y [[Catego...

New page

'''Unreleased structure'''

The entry 5b4k is ON HOLD until Paper Publication

Authors: Oki, H., Zama, Y.

Description:
[[Category: Unreleased Structures]]
[[Category: Zama, Y]]
[[Category: Oki, H]]