7w4x - Revision history

OCA at 17:36, 29 November 2023

OCA — Wed, 29 Nov 2023 17:36:10 GMT

←Older revision		Revision as of 17:36, 29 November 2023
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	<StructureSection load='7w4x' size='340' side='right'caption='[[7w4x]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='7w4x' size='340' side='right'caption='[[7w4x]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7w4x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7W4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W4X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7w4x]] 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=7W4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W4X FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8G7:(2R,4S)-2-(2-hydroxyethyl)-2,6-dimethyl-4-(2-methylprop-1-enyl)-3,4-dihydropyrano[3,2-c][1,8]naphthyridin-5-one'>8G7</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]] 2.2000732Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3',5'-cyclic-AMP_phosphodiesterase 3',5'-cyclic-AMP phosphodiesterase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.53 3.1.4.53] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8G7:(2R,4S)-2-(2-hydroxyethyl)-2,6-dimethyl-4-(2-methylprop-1-enyl)-3,4-dihydropyrano[3,2-c][1,8]naphthyridin-5-one'>8G7</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=7w4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w4x OCA], [https://pdbe.org/7w4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w4x RCSB], [https://www.ebi.ac.uk/pdbsum/7w4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w4x 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=7w4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w4x OCA], [https://pdbe.org/7w4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w4x RCSB], [https://www.ebi.ac.uk/pdbsum/7w4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w4x ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN]] Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:[https://omim.org/entry/614613 614613]]. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.<ref>PMID:22464250</ref>	+	[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:[https://omim.org/entry/614613 614613]. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.<ref>PMID:22464250</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</ref>	+	[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 7w4x" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7w4x" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~3',5'-cyclic-AMP phosphodiesterase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Huang, Y Y]]	+	[[Category: Huang Y-Y]]
-	[[Category: Luo, H B]]	+	[[Category: Luo H-B]]
-	~~[[Category: 5'-cyclic phosphodiesterase 4d]]~~	+
-	~~[[Category: Camp-specific 3ss']]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 12:03, 23 March 2022

OCA — Wed, 23 Mar 2022 12:03:21 GMT

←Older revision		Revision as of 12:03, 23 March 2022
Line 1:		Line 1:

	==Crystal structure of PDE4D catalytic domain complexed with 17==		==Crystal structure of PDE4D catalytic domain complexed with 17==
-	<StructureSection load='7w4x' size='340' side='right'caption='[[7w4x]]' scene=''>	+	<StructureSection load='7w4x' size='340' side='right'caption='[[7w4x]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7W4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W4X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7w4x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7W4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W4X FirstGlance]. <br>
-	</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=7w4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w4x OCA], [https://pdbe.org/7w4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w4x RCSB], [https://www.ebi.ac.uk/pdbsum/7w4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w4x ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8G7:(2R,4S)-2-(2-hydroxyethyl)-2,6-dimethyl-4-(2-methylprop-1-enyl)-3,4-dihydropyrano[3,2-c][1,8]naphthyridin-5-one'>8G7</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3',5'-cyclic-AMP_phosphodiesterase 3',5'-cyclic-AMP phosphodiesterase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.53 3.1.4.53] </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=7w4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w4x OCA], [https://pdbe.org/7w4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w4x RCSB], [https://www.ebi.ac.uk/pdbsum/7w4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w4x ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN]] Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:[https://omim.org/entry/614613 614613]]. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.<ref>PMID:22464250</ref>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Psoriasis is a common immune-mediated skin disorder manifesting in abnormal skin plaques, and phosphodiesterase 4 (PDE4) is an effective target for the treatment of inflammatory diseases such as psoriasis. Toddacoumalone is a natural PDE4 inhibitor with moderate potency and imperfect drug-like properties. To discover novel and potent PDE4 inhibitors with considerable druggability, a series of toddacoumalone derivatives were designed and synthesized, leading to the compound (2R,4S)-6-ethyl-2-(2-hydroxyethyl)-2,8-dimethyl-4-(2-methylprop-1-en-1-yl)-2,3,4, 6-tetrahydro-5H-pyrano[3,2-c][1,8]naphthyridin-5-one (33a) with high inhibitory potency (IC50 = 3.1 nM), satisfactory selectivity, favorable skin permeability, and a well-characterized binding mechanism. Encouragingly, topical administration of 33a exhibited remarkable therapeutic effects in an imiquimod-induced psoriasis mouse model.
		+
		+	Discovery and Structural Optimization of Toddacoumalone Derivatives as Novel PDE4 Inhibitors for the Topical Treatment of Psoriasis.,Song Z, Huang YY, Hou KQ, Liu L, Zhou F, Huang Y, Wan G, Luo HB, Xiong XF J Med Chem. 2022 Mar 10;65(5):4238-4254. doi: 10.1021/acs.jmedchem.1c02058. Epub , 2022 Feb 21. PMID:35188767<ref>PMID:35188767</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7w4x" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 3',5'-cyclic-AMP phosphodiesterase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Huang Y-Y]]	+	[[Category: Huang, Y Y]]
-	[[Category: Luo H-B]]	+	[[Category: Luo, H B]]
		+	[[Category: 5'-cyclic phosphodiesterase 4d]]
		+	[[Category: Camp-specific 3ss']]
		+	[[Category: Hydrolase]]

OCA at 06:18, 16 March 2022

OCA — Wed, 16 Mar 2022 06:18:23 GMT

←Older revision		Revision as of 06:18, 16 March 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7w4x ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of PDE4D catalytic domain complexed with 17==
-		+	<StructureSection load='7w4x' size='340' side='right'caption='[[7w4x]]' scene=''>
-	~~Authors~~: ~~Huang~~, Y.-Y., ~~Luo~~, H.-B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7W4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W4X FirstGlance]. <br>
-	~~Description: Crystal structure of PDE4D catalytic domain complexed with 17~~	+	</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=7w4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w4x OCA], [https://pdbe.org/7w4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w4x RCSB], [https://www.ebi.ac.uk/pdbsum/7w4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w4x ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Luo, H.~~-B]]	+	__TOC__
-	[[Category: ~~Huang, Y.~~-Y]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Huang Y-Y]]
		+	[[Category: Luo H-B]]

OCA at 08:42, 12 January 2022

OCA — Wed, 12 Jan 2022 08:42:11 GMT

←Older revision		Revision as of 08:42, 12 January 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7w4x is ON HOLD	+	The entry 7w4x is ON HOLD until Paper Publication

	Authors: Huang, Y.-Y., Luo, H.-B.		Authors: Huang, Y.-Y., Luo, H.-B.

OCA: Protected "7w4x" [edit=sysop:move=sysop]

OCA — Wed, 08 Dec 2021 08:44:36 GMT

Protected "7w4x" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:44, 8 December 2021

OCA: New page: '''Unreleased structure''' The entry 7w4x is ON HOLD Authors: Huang, Y.-Y., Luo, H.-B. Description: Crystal structure of PDE4D catalytic domain complexed with 17 [[Category: Unreleased...

OCA — Wed, 08 Dec 2021 08:44:35 GMT

New page: '''Unreleased structure''' The entry 7w4x is ON HOLD Authors: Huang, Y.-Y., Luo, H.-B. Description: Crystal structure of PDE4D catalytic domain complexed with 17 [[Category: Unreleased...

New page

'''Unreleased structure'''

The entry 7w4x is ON HOLD

Authors: Huang, Y.-Y., Luo, H.-B.

Description: Crystal structure of PDE4D catalytic domain complexed with 17
[[Category: Unreleased Structures]]
[[Category: Luo, H.-B]]
[[Category: Huang, Y.-Y]]