1y2c: Difference between revisions

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{{Seed}}
[[Image:1y2c.png|left|200px]]


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==Catalytic Domain Of Human Phosphodiesterase 4D In Complex With 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester==
The line below this paragraph, containing "STRUCTURE_1y2c", creates the "Structure Box" on the page.
<StructureSection load='1y2c' size='340' side='right'caption='[[1y2c]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1y2c]] 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=1Y2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y2C FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DE:3,5-DIMETHYL-1-PHENYL-1H-PYRAZOLE-4-CARBOXYLIC+ACID+ETHYL+ESTER'>3DE</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>
{{STRUCTURE_1y2c| PDB=1y2c |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1y2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y2c OCA], [https://pdbe.org/1y2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y2c RCSB], [https://www.ebi.ac.uk/pdbsum/1y2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y2c ProSAT]</span></td></tr>
</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/y2/1y2c_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=1y2c ConSurf].
<div style="clear:both"></div>


===Catalytic Domain Of Human Phosphodiesterase 4D In Complex With 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester===
==See Also==
 
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 
== References ==
<!--
<references/>
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(as it appears on PubMed at http://www.pubmed.gov), where 15685167 is the PubMed ID number.
</StructureSection>
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{{ABSTRACT_PUBMED_15685167}}
 
==About this Structure==
1Y2C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y2C OCA].
 
==Reference==
A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design., Card GL, Blasdel L, England BP, Zhang C, Suzuki Y, Gillette S, Fong D, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY, Nat Biotechnol. 2005 Feb;23(2):201-7. Epub 2005 Jan 30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15685167 15685167]
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Artis, D R.]]
[[Category: Artis DR]]
[[Category: Blasdel, L.]]
[[Category: Blasdel L]]
[[Category: Bollag, G.]]
[[Category: Bollag G]]
[[Category: Card, G L.]]
[[Category: Card GL]]
[[Category: England, B P.]]
[[Category: England BP]]
[[Category: Fong, D.]]
[[Category: Fong D]]
[[Category: Gillette, S.]]
[[Category: Gillette S]]
[[Category: Ibrahim, P N.]]
[[Category: Ibrahim PN]]
[[Category: Kim, S H.]]
[[Category: Kim S-H]]
[[Category: Milburn, M V.]]
[[Category: Milburn MV]]
[[Category: Schlessinger, J.]]
[[Category: Schlessinger J]]
[[Category: Suzuki, Y.]]
[[Category: Suzuki Y]]
[[Category: Zhang, C.]]
[[Category: Zhang C]]
[[Category: Zhang, K Y.J.]]
[[Category: Zhang KYJ]]
[[Category: Pde]]
[[Category: Pde4d]]
[[Category: Phosphodiesterase]]
[[Category: Pyrazole]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:27:49 2008''

Latest revision as of 11:54, 14 February 2024

Catalytic Domain Of Human Phosphodiesterase 4D In Complex With 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl esterCatalytic Domain Of Human Phosphodiesterase 4D In Complex With 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester

Structural highlights

1y2c is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.67Å
Ligands:, , ,
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.

See Also

References

  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:http://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:http://dx.doi.org/10.1016/j.str.2004.10.004

1y2c, resolution 1.67Å

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