2pw3
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(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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Revision as of 21:21, 12 November 2007
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Structure of the PDE4D-cAMP complex
Contents |
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.
Disease
Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[600129]
About this Structure
2PW3 is a Single protein structure of sequence from Homo sapiens with ZN and CMP 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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