5k32 - Revision history

OCA at 10:38, 27 September 2023

OCA — Wed, 27 Sep 2023 10:38:47 GMT

←Older revision		Revision as of 10:38, 27 September 2023
Line 1:		Line 1:

	==PDE4D crystal structure in complex with small molecule inhibitor==		==PDE4D crystal structure in complex with small molecule inhibitor==
-	<StructureSection load='5k32' size='340' side='right' caption='[[5k32]], [[Resolution\|resolution]] 1.99Å' scene=''>	+	<StructureSection load='5k32' size='340' side='right'caption='[[5k32]], [[Resolution\|resolution]] 1.99Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5k32]] 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=5K32 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5K32 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5k32]] 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=5K32 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K32 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6Q2:4-[(3-METHOXYPHENYL)AMINO]-2-PHENYL-7,8-DIHYDRO-1,6-NAPHTHYRIDIN-5(6H)-ONE'>6Q2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.99Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE4D, DPDE3 ([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=6Q2:4-[(3-METHOXYPHENYL)AMINO]-2-PHENYL-7,8-DIHYDRO-1,6-NAPHTHYRIDIN-5(6H)-ONE'>6Q2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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'>[http://en.wikipedia.org/wiki/3',5'-cyclic-AMP_phosphodiesterase 3',5'-cyclic-AMP phosphodiesterase], with EC number [http://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=5k32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k32 OCA], [https://pdbe.org/5k32 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k32 RCSB], [https://www.ebi.ac.uk/pdbsum/5k32 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k32 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=5k32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k32 OCA], [~~http~~://pdbe.org/5k32 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5k32 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5k32 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5k32 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://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:[~~http~~://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 ==
-	[~~[http~~://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 24:		Line 23:

	==See Also==		==See Also==
-	*[[Phosphodiesterase\|Phosphodiesterase]]	+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~3',5'-cyclic-AMP phosphodiesterase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Aymami, J]]	+	[[Category: Aymami J]]
-	[[Category: Bonin, I]]	+	[[Category: Bonin I]]
-	[[Category: Gracia, J]]	+	[[Category: Gracia J]]
-	[[Category: Hernandez, B]]	+	[[Category: Hernandez B]]
-	[[Category: Roberts, R]]	+	[[Category: Roberts R]]
-	[[Category: Segarra, V]]	+	[[Category: Segarra V]]
-	[[Category: Soler, M]]	+	[[Category: Soler M]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Phosphodiesterase~~]]	+

OCA at 07:52, 21 March 2018

OCA — Wed, 21 Mar 2018 07:52:09 GMT

←Older revision		Revision as of 07:52, 21 March 2018
Line 3:		Line 3:
	<StructureSection load='5k32' size='340' side='right' caption='[[5k32]], [[Resolution\|resolution]] 1.99Å' scene=''>		<StructureSection load='5k32' size='340' side='right' caption='[[5k32]], [[Resolution\|resolution]] 1.99Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5k32]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K32 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5k32]] 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=5K32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K32 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6Q2:4-[(3-METHOXYPHENYL)AMINO]-2-PHENYL-7,8-DIHYDRO-1,6-NAPHTHYRIDIN-5(6H)-ONE'>6Q2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6Q2:4-[(3-METHOXYPHENYL)AMINO]-2-PHENYL-7,8-DIHYDRO-1,6-NAPHTHYRIDIN-5(6H)-ONE'>6Q2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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">PDE4D, DPDE3 ([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-AMP_phosphodiesterase 3',5'-cyclic-AMP phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.53 3.1.4.53] </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-AMP_phosphodiesterase 3',5'-cyclic-AMP phosphodiesterase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5k32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k32 OCA], [http://pdbe.org/5k32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k32 RCSB], [http://www.ebi.ac.uk/pdbsum/5k32 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k32 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=5k32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k32 OCA], [http://pdbe.org/5k32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k32 RCSB], [http://www.ebi.ac.uk/pdbsum/5k32 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k32 ProSAT]</span></td></tr>
Line 12:		Line 13:
	== Function ==		== Function ==
	[[http://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>		[[http://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 ==
		+	Rational design of a novel template of naphthyridinones rapidly led to PDE4 inhibitors with subnanomolar enzymatic potencies. X-ray crystallography confirmed the binding mode of this novel template. We achieved compounds with double-digit picomolar enzymatic potencies through further structure-based design by targeting both the PDE4 enzyme metal-binding pocket and occupying the solvent-filled pocket. A strategy for lung retention and long duration of action based on low aqueous solubility was followed. In vivo efficacies were measured in a rat lung neutrophilia model by suspension microspray and dry powder administration. Suspension microspray of potent compounds showed in vivo efficacy with a clear dose-response. Despite sustained lung levels, dry powder administration performed much less well and without proper dose-response, highlighting clear differences between the two formulations. This indicates a deficiency in the low aqueous solubility strategy for long duration lung efficacy.
		+
		+	4-Amino-7,8-dihydro-1,6-naphthyridin-5(6 H)-ones as Inhaled Phosphodiesterase Type 4 (PDE4) Inhibitors: Structural Biology and Structure-Activity Relationships.,Roberts RS, Sevilla S, Ferrer M, Taltavull J, Hernandez B, Segarra V, Gracia J, Lehner MD, Gavalda A, Andres M, Cabedo J, Vilella D, Eichhorn P, Calama E, Carcasona C, Miralpeix M J Med Chem. 2018 Mar 13. doi: 10.1021/acs.jmedchem.7b01751. PMID:29502405<ref>PMID:29502405</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5k32" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphodiesterase\|Phosphodiesterase]]
	== References ==		== References ==
	<references/>		<references/>
Line 17:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: 3',5'-cyclic-AMP phosphodiesterase]]		[[Category: 3',5'-cyclic-AMP phosphodiesterase]]
		+	[[Category: Human]]
	[[Category: Aymami, J]]		[[Category: Aymami, J]]
	[[Category: Bonin, I]]		[[Category: Bonin, I]]

OCA at 13:46, 29 March 2017

OCA — Wed, 29 Mar 2017 13:46:14 GMT

←Older revision		Revision as of 13:46, 29 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5k32 ~~is ON HOLD until Paper Publication~~	+	==PDE4D crystal structure in complex with small molecule inhibitor==
-		+	<StructureSection load='5k32' size='340' side='right' caption='[[5k32]], [[Resolution\|resolution]] 1.99Å' scene=''>
-	~~Authors~~: ~~Segarra, V~~., ~~Hernandez~~, B., ~~Roberts~~, R., ~~Gracia~~, J., ~~Soler~~, M., ~~Bonin~~, I., ~~Aymami~~, J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5k32]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K32 FirstGlance]. <br>
-	~~Description~~: PDE4D ~~crystal structure~~ in ~~complex~~ with small ~~molecule inhibitor~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6Q2:4-[(3-METHOXYPHENYL)AMINO]-2-PHENYL-7,8-DIHYDRO-1,6-NAPHTHYRIDIN-5(6H)-ONE'>6Q2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-AMP_phosphodiesterase 3',5'-cyclic-AMP phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.53 3.1.4.53] </span></td></tr>
-	[[Category: ~~Segarra~~, V]]	+	<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=5k32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k32 OCA], [http://pdbe.org/5k32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k32 RCSB], [http://www.ebi.ac.uk/pdbsum/5k32 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k32 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://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:[http://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 ==
		+	[[http://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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: 3',5'-cyclic-AMP phosphodiesterase]]
	[[Category: Aymami, J]]		[[Category: Aymami, J]]
	[[Category: Bonin, I]]		[[Category: Bonin, I]]
		+	[[Category: Gracia, J]]
	[[Category: Hernandez, B]]		[[Category: Hernandez, B]]
-	[[Category: Gracia, J]]
	[[Category: Roberts, R]]		[[Category: Roberts, R]]
		+	[[Category: Segarra, V]]
	[[Category: Soler, M]]		[[Category: Soler, M]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Phosphodiesterase]]

OCA at 10:08, 9 March 2017

OCA — Thu, 09 Mar 2017 10:08:57 GMT

←Older revision		Revision as of 10:08, 9 March 2017
Line 7:		Line 7:
	Description: PDE4D crystal structure in complex with small molecule inhibitor		Description: PDE4D crystal structure in complex with small molecule inhibitor
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Segarra, V]]
	[[Category: Aymami, J]]		[[Category: Aymami, J]]
	[[Category: Bonin, I]]		[[Category: Bonin, I]]
	[[Category: Hernandez, B]]		[[Category: Hernandez, B]]
		+	[[Category: Gracia, J]]
	[[Category: Roberts, R]]		[[Category: Roberts, R]]
	[[Category: Soler, M]]		[[Category: Soler, M]]
-	[[Category: Segarra, V]]
-	[[Category: Gracia, J]]

OCA: Protected "5k32" [edit=sysop:move=sysop]

OCA — Wed, 01 Jun 2016 14:15:00 GMT

Protected "5k32" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:15, 1 June 2016

OCA: New page: '''Unreleased structure''' The entry 5k32 is ON HOLD until Paper Publication Authors: Segarra, V., Hernandez, B., Roberts, R., Gracia, J., Soler, M., Bonin, I., Aymami, J. Description:...

OCA — Wed, 01 Jun 2016 14:14:59 GMT

New page: '''Unreleased structure''' The entry 5k32 is ON HOLD until Paper Publication Authors: Segarra, V., Hernandez, B., Roberts, R., Gracia, J., Soler, M., Bonin, I., Aymami, J. Description:...

New page

'''Unreleased structure'''

The entry 5k32 is ON HOLD until Paper Publication

Authors: Segarra, V., Hernandez, B., Roberts, R., Gracia, J., Soler, M., Bonin, I., Aymami, J.

Description: PDE4D crystal structure in complex with small molecule inhibitor
[[Category: Unreleased Structures]]
[[Category: Aymami, J]]
[[Category: Bonin, I]]
[[Category: Hernandez, B]]
[[Category: Roberts, R]]
[[Category: Soler, M]]
[[Category: Segarra, V]]
[[Category: Gracia, J]]