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== | ==Crystal structure of Human Phosphodiesterase 5 complexed with tadalafil(Cialis)== | ||
<StructureSection load='1udu' size='340' side='right'caption='[[1udu]], [[Resolution|resolution]] 2.83Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1udu]] 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=1UDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UDU 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]] 2.83Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIA:6-BENZO[1,3]DIOXOL-5-YL-2-METHYL-2,3,6,7,12,12A-HEXAHYDRO-PYRAZINO[1,2 1,6]PYRIDO[3,4-B]INDOLE-1,4-DIONE'>CIA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=1udu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1udu OCA], [https://pdbe.org/1udu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1udu RCSB], [https://www.ebi.ac.uk/pdbsum/1udu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1udu 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/ud/1udu_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=1udu ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles. | Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles. | ||
Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.,Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM Nature. 2003 Sep 4;425(6953):98-102. PMID:12955149<ref>PMID:12955149</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 1udu" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Cho | [[Category: Cho JM]] | ||
[[Category: Eum | [[Category: Eum SJ]] | ||
[[Category: Heo | [[Category: Heo Y-S]] | ||
[[Category: Hwang | [[Category: Hwang KY]] | ||
[[Category: Hyun | [[Category: Hyun Y-L]] | ||
[[Category: Jeon | [[Category: Jeon YH]] | ||
[[Category: Kim | [[Category: Kim E]] | ||
[[Category: Kim | [[Category: Kim JH]] | ||
[[Category: Lee | [[Category: Lee J-O]] | ||
[[Category: Lee | [[Category: Lee JI]] | ||
[[Category: Lee | [[Category: Lee TG]] | ||
[[Category: Moon | [[Category: Moon J]] | ||
[[Category: Park | [[Category: Park S-Y]] | ||
[[Category: Ro | [[Category: Ro S]] | ||
[[Category: Sung | [[Category: Sung B-J]] | ||
[[Category: Yoon | [[Category: Yoon JM]] | ||
Latest revision as of 02:51, 28 December 2023
Crystal structure of Human Phosphodiesterase 5 complexed with tadalafil(Cialis)Crystal structure of Human Phosphodiesterase 5 complexed with tadalafil(Cialis)
Structural highlights
FunctionPDE5A_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. Publication Abstract from PubMedPhosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles. Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.,Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM Nature. 2003 Sep 4;425(6953):98-102. PMID:12955149[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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