6f6u - Revision history

OCA at 07:49, 23 May 2018

2018-05-23T07:49:35Z

←Older revision		Revision as of 07:49, 23 May 2018
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	<StructureSection load='6f6u' size='340' side='right' caption='[[6f6u]], [[Resolution\|resolution]] 1.83Å' scene=''>		<StructureSection load='6f6u' size='340' side='right' caption='[[6f6u]], [[Resolution\|resolution]] 1.83Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6f6u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F6U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6f6u]] 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=6F6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F6U FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CV8:2-[(~{E})-(3-cyclopentyloxy-4-methoxy-phenyl)methylideneamino]oxy-1-[(2~{R},6~{S})-2,6-dimethylmorpholin-4-yl]ethanone'>CV8</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=CV8:2-[(~{E})-(3-cyclopentyloxy-4-methoxy-phenyl)methylideneamino]oxy-1-[(2~{R},6~{S})-2,6-dimethylmorpholin-4-yl]ethanone'>CV8</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f6u OCA], [http://pdbe.org/6f6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f6u RCSB], [http://www.ebi.ac.uk/pdbsum/6f6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f6u 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=6f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f6u OCA], [http://pdbe.org/6f6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f6u RCSB], [http://www.ebi.ac.uk/pdbsum/6f6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f6u ProSAT]</span></td></tr>
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	</StructureSection>		</StructureSection>
	[[Category: 3',5'-cyclic-AMP phosphodiesterase]]		[[Category: 3',5'-cyclic-AMP phosphodiesterase]]
		+	[[Category: Human]]
	[[Category: Donini, S]]		[[Category: Donini, S]]
	[[Category: Parisini, E]]		[[Category: Parisini, E]]

OCA at 05:35, 16 May 2018

2018-05-16T05:35:00Z

←Older revision		Revision as of 05:35, 16 May 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6f6u is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the PDE4D catalytic domain in complex with GEBR-7b==
		+	<StructureSection load='6f6u' size='340' side='right' caption='[[6f6u]], [[Resolution\|resolution]] 1.83Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6f6u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F6U FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CV8:2-[(~{E})-(3-cyclopentyloxy-4-methoxy-phenyl)methylideneamino]oxy-1-[(2~{R},6~{S})-2,6-dimethylmorpholin-4-yl]ethanone'>CV8</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6f6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f6u OCA], [http://pdbe.org/6f6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f6u RCSB], [http://www.ebi.ac.uk/pdbsum/6f6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f6u 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Selected members of the large rolipram-related GEBR family of type 4 phosphodiesterase (PDE4) inhibitors have been shown to facilitate long-term potentiation and to improve memory functions without causing emetic-like behavior in rodents. Despite their micromolar-range binding affinities and their promising pharmacological and toxicological profiles, few if any structure-activity relationship studies have been performed to elucidate the molecular bases of their action. Here, we report the crystal structure of a number of GEBR library compounds in complex with the catalytic domain of PDE4D as well as their inhibitory profiles for both the long PDE4D3 isoform and the catalytic domain alone. Furthermore, we assessed the stability of the observed ligand conformations in the context of the intact enzyme using molecular dynamics simulations. The longer and more flexible ligands appear to be capable of forming contacts with the regulatory portion of the enzyme, thus possibly allowing some degree of selectivity between the different PDE4 isoforms.

-	~~Authors~~:	+	Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds.,Prosdocimi T, Mollica L, Donini S, Semrau MS, Lucarelli AP, Aiolfi E, Cavalli A, Storici P, Alfei S, Brullo C, Bruno O, Parisini E Biochemistry. 2018 May 15;57(19):2876-2888. doi: 10.1021/acs.biochem.8b00288., Epub 2018 May 1. PMID:29652483<ref>PMID:29652483</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6f6u" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: 3',5'-cyclic-AMP phosphodiesterase]]
		+	[[Category: Donini, S]]
		+	[[Category: Parisini, E]]
		+	[[Category: Prosdocimi, T]]
		+	[[Category: Catalytic domain]]
		+	[[Category: Gebr]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Pde4]]

OCA at 05:08, 20 December 2017

2017-12-20T05:08:55Z

←Older revision		Revision as of 05:08, 20 December 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6f6u is ON HOLD	+	The entry 6f6u is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6f6u" [edit=sysop:move=sysop]

2017-12-13T06:03:09Z

Protected "6f6u" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:03, 13 December 2017

OCA: New page: '''Unreleased structure''' The entry 6f6u is ON HOLD Authors: Description: Category: Unreleased Structures

2017-12-13T06:03:07Z

New page: '''Unreleased structure''' The entry 6f6u is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6f6u is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]