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[[Image:1xp0.gif|left|200px]]<br /><applet load="1xp0" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1xp0, resolution 1.79&Aring;" />
'''Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil'''<br />


==Overview==
==Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil==
Phosphodiesterases (PDEs) comprise a large family of enzymes that catalyze the hydrolysis of cAMP or cGMP and are implicated in various diseases. We describe the high-resolution crystal structures of the catalytic domains of PDE4B, PDE4D, and PDE5A with ten different inhibitors, including the drug candidates cilomilast and roflumilast, for respiratory diseases. These cocrystal structures reveal a common scheme of inhibitor binding to the PDEs: (i) a hydrophobic clamp formed by highly conserved hydrophobic residues that sandwich the inhibitor in the active site; (ii) hydrogen bonding to an invariant glutamine that controls the orientation of inhibitor binding. A scaffold can be readily identified for any given inhibitor based on the formation of these two types of conserved interactions. These structural insights will enable the design of isoform-selective inhibitors with improved binding affinity and should facilitate the discovery of more potent and selective PDE inhibitors for the treatment of a variety of diseases.
<StructureSection load='1xp0' size='340' side='right'caption='[[1xp0]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xp0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The August 2012 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''cAMP-dependent Protein Kinase (PKA)''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2012_8 10.2210/rcsb_pdb/mom_2012_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XP0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.79&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VDN:2-{2-ETHOXY-5-[(4-ETHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}-5-METHYL-7-PROPYLIMIDAZO[5,1-F][1,2,4]TRIAZIN-4(1H)-ONE'>VDN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xp0 OCA], [https://pdbe.org/1xp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xp0 RCSB], [https://www.ebi.ac.uk/pdbsum/1xp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xp0 ProSAT]</span></td></tr>
</table>
== Function ==
[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.
== 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/xp/1xp0_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=1xp0 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1XP0 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=VDN:'>VDN</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=1XP0 OCA].
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Structural basis for the activity of drugs that inhibit phosphodiesterases., 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, Structure. 2004 Dec;12(12):2233-47. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15576036 15576036]
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Artis, D R.]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Bollag, G.]]
[[Category: Artis DR]]
[[Category: Card, G L.]]
[[Category: Bollag G]]
[[Category: England, B P.]]
[[Category: Card GL]]
[[Category: Fong, D.]]
[[Category: England BP]]
[[Category: Gillette, S.]]
[[Category: Fong D]]
[[Category: Ibrahim, P N.]]
[[Category: Gillette S]]
[[Category: Kim, S H.]]
[[Category: Ibrahim PN]]
[[Category: Lee, B.]]
[[Category: Kim S-H]]
[[Category: Luu, C.]]
[[Category: Lee B]]
[[Category: Milburn, M V.]]
[[Category: Luu C]]
[[Category: Powell, B.]]
[[Category: Milburn MV]]
[[Category: Schlessinger, J.]]
[[Category: Powell B]]
[[Category: Suzuki, Y.]]
[[Category: Schlessinger J]]
[[Category: Tabrizizad, M.]]
[[Category: Suzuki Y]]
[[Category: Zhang, K Y.J.]]
[[Category: Tabrizizad M]]
[[Category: MG]]
[[Category: Zhang KYJ]]
[[Category: VDN]]
[[Category: ZN]]
[[Category: levitra]]
[[Category: pde]]
[[Category: pde5a]]
[[Category: phosphodiesterase]]
[[Category: vardenafil]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:57:06 2008''

Latest revision as of 11:52, 14 February 2024

Catalytic Domain Of Human Phosphodiesterase 5A In Complex With VardenafilCatalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil

Structural highlights

1xp0 is a 1 chain structure with sequence from Homo sapiens. The August 2012 RCSB PDB Molecule of the Month feature on cAMP-dependent Protein Kinase (PKA) by David Goodsell is 10.2210/rcsb_pdb/mom_2012_8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.79Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

Evolutionary Conservation

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

See Also

1xp0, resolution 1.79Å

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