2pw3
From Proteopedia
(New page: 200px<br /> <applet load="2pw3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pw3, resolution 1.56Å" /> '''Structure of the PD...) |
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| - | [[Image:2pw3.gif|left|200px]]<br /> | + | [[Image:2pw3.gif|left|200px]]<br /><applet load="2pw3" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2pw3" size=" | + | |
caption="2pw3, resolution 1.56Å" /> | caption="2pw3, resolution 1.56Å" /> | ||
'''Structure of the PDE4D-cAMP complex'''<br /> | '''Structure of the PDE4D-cAMP complex'''<br /> | ||
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==Overview== | ==Overview== | ||
Phosphodiesterases (PDEs) are key enzymes that control the cellular, concentrations of the second messengers cAMP and cGMP. The mechanism for, selective recognition of substrates cAMP and cGMP by individual PDE, families remains a puzzle. To understand the mechanism for substrate, recognition by PDE enzymes, the crystal structure of the catalytic domain, of an inactive D201N mutant of PDE4D2 in complex with substrate cAMP has, been determined at 1.56 A resolution. The structure shows that Gln369, forms only one hydrogen bond with the adenine of cAMP. This finding, provides experimental evidence against the hypothesis of two hydrogen, bonds between the invariant glutamine and the substrate cAMP in PDE4, and, thus suggests that the widely circulated "glutamine switch" model is, unlikely the mechanism for substrate recognition by PDEs. A structure, comparison between PDE4D2-cAMP and PDE10A2-cAMP reveals an anti, configuration of cAMP in PDE4D2 but syn in PDE10A2, in addition to, different contact patterns of cAMP in these two structures. These, observations imply that individual PDE families have their characteristic, mechanisms for substrate recognition. | Phosphodiesterases (PDEs) are key enzymes that control the cellular, concentrations of the second messengers cAMP and cGMP. The mechanism for, selective recognition of substrates cAMP and cGMP by individual PDE, families remains a puzzle. To understand the mechanism for substrate, recognition by PDE enzymes, the crystal structure of the catalytic domain, of an inactive D201N mutant of PDE4D2 in complex with substrate cAMP has, been determined at 1.56 A resolution. The structure shows that Gln369, forms only one hydrogen bond with the adenine of cAMP. This finding, provides experimental evidence against the hypothesis of two hydrogen, bonds between the invariant glutamine and the substrate cAMP in PDE4, and, thus suggests that the widely circulated "glutamine switch" model is, unlikely the mechanism for substrate recognition by PDEs. A structure, comparison between PDE4D2-cAMP and PDE10A2-cAMP reveals an anti, configuration of cAMP in PDE4D2 but syn in PDE10A2, in addition to, different contact patterns of cAMP in these two structures. These, observations imply that individual PDE families have their characteristic, mechanisms for substrate recognition. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600129 600129]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2PW3 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 ZN and CMP 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:// | + | 2PW3 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> and <scene name='pdbligand=CMP:'>CMP</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=2PW3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: substrate specificity]] | [[Category: substrate specificity]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:43:39 2008'' |
Revision as of 10:43, 23 January 2008
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Structure of the PDE4D-cAMP complex
Overview
Phosphodiesterases (PDEs) are key enzymes that control the cellular, concentrations of the second messengers cAMP and cGMP. The mechanism for, selective recognition of substrates cAMP and cGMP by individual PDE, families remains a puzzle. To understand the mechanism for substrate, recognition by PDE enzymes, the crystal structure of the catalytic domain, of an inactive D201N mutant of PDE4D2 in complex with substrate cAMP has, been determined at 1.56 A resolution. The structure shows that Gln369, forms only one hydrogen bond with the adenine of cAMP. This finding, provides experimental evidence against the hypothesis of two hydrogen, bonds between the invariant glutamine and the substrate cAMP in PDE4, and, thus suggests that the widely circulated "glutamine switch" model is, unlikely the mechanism for substrate recognition by PDEs. A structure, comparison between PDE4D2-cAMP and PDE10A2-cAMP reveals an anti, configuration of cAMP in PDE4D2 but syn in PDE10A2, in addition to, different contact patterns of cAMP in these two structures. These, observations imply that individual PDE families have their characteristic, mechanisms for substrate recognition.
About this Structure
2PW3 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Full crystallographic information is available from OCA.
Reference
The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10., Wang H, Robinson H, Ke H, J Mol Biol. 2007 Aug 10;371(2):302-7. Epub 2007 May 26. PMID:17582435
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