1q9m: Difference between revisions

Latest revision as of 08:14, 14 February 2024

Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity

Structural highlights

1q9m is a 4 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1oym. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	ROL, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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: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.^[1]

Function

PDE4D_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V. Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. Am J Hum Genet. 2012 Apr 6;90(4):740-5. doi: 10.1016/j.ajhg.2012.03.003. Epub, 2012 Mar 29. PMID:22464250 doi:10.1016/j.ajhg.2012.03.003
↑ Zhang KY, Card GL, Suzuki Y, Artis DR, Fong D, Gillette S, Hsieh D, Neiman J, West BL, Zhang C, Milburn MV, Kim SH, Schlessinger J, Bollag G. A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell. 2004 Jul 23;15(2):279-86. PMID:15260978 doi:https://dx.doi.org/10.1016/j.molcel.2004.07.005
↑ Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY. Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004 Dec;12(12):2233-47. PMID:15576036 doi:https://dx.doi.org/10.1016/j.str.2004.10.004

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V. Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. Am J Hum Genet. 2012 Apr 6;90(4):740-5. doi: 10.1016/j.ajhg.2012.03.003. Epub, 2012 Mar 29. PMID:22464250 doi:10.1016/j.ajhg.2012.03.003

[2] Zhang KY, Card GL, Suzuki Y, Artis DR, Fong D, Gillette S, Hsieh D, Neiman J, West BL, Zhang C, Milburn MV, Kim SH, Schlessinger J, Bollag G. A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell. 2004 Jul 23;15(2):279-86. PMID:15260978 doi:https://dx.doi.org/10.1016/j.molcel.2004.07.005

[3] Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY. Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004 Dec;12(12):2233-47. PMID:15576036 doi:https://dx.doi.org/10.1016/j.str.2004.10.004

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-[[Image:1q9m.png|left|200px]]
-{{STRUCTURE_1q9m|  PDB=1q9m  |  SCENE=  }}
+==Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity==
+<StructureSection load='1q9m' size='340' side='right'caption='[[1q9m]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-===Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity===
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1q9m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1oym 1oym]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q9M FirstGlance]. <br>
-{{ABSTRACT_PUBMED_12842049}}
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ROL:ROLIPRAM'>ROL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-==About this Structure==
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q9m OCA], [https://pdbe.org/1q9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q9m RCSB], [https://www.ebi.ac.uk/pdbsum/1q9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q9m ProSAT]</span></td></tr>
-[[1q9m]] is a 4 chain structure of [[Phosphodiesterase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1oym 1oym]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q9M OCA].
+</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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q9/1q9m_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1q9m ConSurf].
+<div style="clear:both"></div>
 ==See Also==
-*[[Phosphodiesterase|Phosphodiesterase]]
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:012842049</ref><references group="xtra"/>
+__TOC__
-[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Huai, Q.]]
+[[Category: Large Structures]]
-[[Category: Ke, H.]]
+[[Category: Huai Q]]
-[[Category: Kim, H Y.]]
+[[Category: Ke H]]
-[[Category: Liu, Y.]]
+[[Category: Kim HY]]
-[[Category: Sun, Y.]]
+[[Category: Liu Y]]
-[[Category: Wang, H.]]
+[[Category: Sun Y]]
-[[Category: Hydrolase]]
+[[Category: Wang H]]
-[[Category: Pde]]
-[[Category: Rolipram]]
-[[Category: Specific inhibitor]]

1q9m: Difference between revisions

Latest revision as of 08:14, 14 February 2024

Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity

Structural highlights

Disease

Function

Evolutionary Conservation

See Also

References

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