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| - | [[Image:1tb7.gif|left|200px]] | |
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| - | {{Structure
| + | ==Catalytic Domain Of Human Phosphodiesterase 4D In Complex With AMP== |
| - | |PDB= 1tb7 |SIZE=350|CAPTION= <scene name='initialview01'>1tb7</scene>, resolution 1.63Å
| + | <StructureSection load='1tb7' size='340' side='right'caption='[[1tb7]], [[Resolution|resolution]] 1.63Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</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> | + | <table><tr><td colspan='2'>[[1tb7]] 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=1TB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TB7 FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.63Å</td></tr> |
| - | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</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> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1tb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tb7 OCA], [https://pdbe.org/1tb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tb7 RCSB], [https://www.ebi.ac.uk/pdbsum/1tb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tb7 ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[1t9r|1T9R]], [[1t9s|1T9S]], [[1taz|1TAZ]], [[1tb5|1TB5]], [[1tbb|1TBB]], [[1tbf|1TBF]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tb7 OCA], [http://www.ebi.ac.uk/pdbsum/1tb7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tb7 RCSB]</span>
| + | == 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/1tb7_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=1tb7 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Catalytic Domain Of Human Phosphodiesterase 4D In Complex With AMP'''
| + | ==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== | + | |
| - | 1TB7 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=1TB7 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]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:53:46 2008''
| + | |
| Structural highlights
1tb7 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 1.63Å |
| 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
- ↑ 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:http://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:http://dx.doi.org/10.1016/j.str.2004.10.004
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