1t9s

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[[Image:1t9s.gif|left|200px]]<br /><applet load="1t9s" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1t9s, resolution 2.00&Aring;" />
 
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'''Catalytic Domain Of Human Phosphodiesterase 5A in Complex with GMP'''<br />
 
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==Overview==
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==Catalytic Domain Of Human Phosphodiesterase 5A in Complex with GMP==
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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.
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<StructureSection load='1t9s' size='340' side='right'caption='[[1t9s]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1t9s]] 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=1T9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T9S FirstGlance]. <br>
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</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&#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=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t9s OCA], [https://pdbe.org/1t9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t9s RCSB], [https://www.ebi.ac.uk/pdbsum/1t9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t9s ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PDE5A_HUMAN PDE5A_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t9/1t9s_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1t9s ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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:15260978<ref>PMID:15260978</ref>
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1T9S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=5GP:'>5GP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T9S OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15260978 15260978]
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</div>
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[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
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<div class="pdbe-citations 1t9s" style="background-color:#fffaf0;"></div>
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[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Artis, D.R.]]
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[[Category: Bollag, G.]]
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[[Category: Card, G.L.]]
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[[Category: Fong, D.]]
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[[Category: Gillette, S.]]
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[[Category: Hsieh, D.]]
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[[Category: Kim, S.H.]]
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[[Category: Milburn, M.V.]]
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[[Category: Neiman, J.]]
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[[Category: Schlessinger, J.]]
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[[Category: Suzuki, Y.]]
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[[Category: West, B.L.]]
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[[Category: Zhang, C.]]
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[[Category: Zhang, K.Y.J.]]
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[[Category: 5GP]]
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[[Category: MG]]
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[[Category: ZN]]
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[[Category: hydrolase]]
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[[Category: pde5a]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:55:56 2008''
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==See Also==
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*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Artis DR]]
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[[Category: Bollag G]]
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[[Category: Card GL]]
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[[Category: Fong D]]
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[[Category: Gillette S]]
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[[Category: Hsieh D]]
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[[Category: Kim S-H]]
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[[Category: Milburn MV]]
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[[Category: Neiman J]]
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[[Category: Schlessinger J]]
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[[Category: Suzuki Y]]
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[[Category: West BL]]
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[[Category: Zhang C]]
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[[Category: Zhang KYJ]]

Current revision

Catalytic Domain Of Human Phosphodiesterase 5A in Complex with GMP

PDB ID 1t9s

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