1tbb: Difference between revisions

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[[Image:1tbb.gif|left|200px]]


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==Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Rolipram==
The line below this paragraph, containing "STRUCTURE_1tbb", creates the "Structure Box" on the page.
<StructureSection load='1tbb' size='340' side='right'caption='[[1tbb]], [[Resolution|resolution]] 1.60&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'>[[1tbb]] 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=1TBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TBB 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]] 1.6&#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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ROL:ROLIPRAM'>ROL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
{{STRUCTURE_1tbb| PDB=1tbb |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1tbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tbb OCA], [https://pdbe.org/1tbb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tbb RCSB], [https://www.ebi.ac.uk/pdbsum/1tbb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tbb 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/tb/1tbb_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=1tbb ConSurf].
<div style="clear:both"></div>


'''Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Rolipram'''
==See Also==
 
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 
== References ==
==Overview==
<references/>
Phosphodiesterases (PDEs) comprise a family of enzymes that modulate the immune response, inflammation, and memory, among many other functions. There are three types of PDEs: cAMP-specific, cGMP-specific, and dual-specific. Here we describe the mechanism of nucleotide selectivity on the basis of high-resolution co-crystal structures of the cAMP-specific PDE4B and PDE4D with AMP, the cGMP-specific PDE5A with GMP, and the apo-structure of the dual-specific PDE1B. These structures show that an invariant glutamine functions as the key specificity determinant by a "glutamine switch" mechanism for recognizing the purine moiety in cAMP or cGMP. The surrounding residues anchor the glutamine residue in different orientations for cAMP and for cGMP. The PDE1B structure shows that in dual-specific PDEs a key histidine residue may enable the invariant glutamine to toggle between cAMP and cGMP. The structural understanding of nucleotide binding enables the design of new PDE inhibitors that may treat diseases in which cyclic nucleotides play a critical role.
__TOC__
 
</StructureSection>
==About this Structure==
1TBB 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=1TBB OCA].
 
==Reference==
A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases., 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, Mol Cell. 2004 Jul 23;15(2):279-86. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15260978 15260978]
[[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: Bollag, G.]]
[[Category: Bollag G]]
[[Category: Card, G L.]]
[[Category: Card GL]]
[[Category: Fong, D.]]
[[Category: Fong D]]
[[Category: Gillette, S.]]
[[Category: Gillette S]]
[[Category: Hsieh, D.]]
[[Category: Hsieh D]]
[[Category: Kim, S H.]]
[[Category: Kim S-H]]
[[Category: Milburn, M V.]]
[[Category: Milburn MV]]
[[Category: Neiman, J.]]
[[Category: Neiman J]]
[[Category: Schlessinger, J.]]
[[Category: Schlessinger J]]
[[Category: Suzuki, Y.]]
[[Category: Suzuki Y]]
[[Category: West, B L.]]
[[Category: West BL]]
[[Category: Zhang, C.]]
[[Category: Zhang C]]
[[Category: Zhang, K Y.J.]]
[[Category: Zhang KYJ]]
[[Category: Pde4d]]
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