1xon: Difference between revisions
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New page: left|200px<br /> <applet load="1xon" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xon, resolution 1.72Å" /> '''Catalytic Domain Of... |
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[[Image:1xon.gif|left|200px]]<br /> | [[Image:1xon.gif|left|200px]]<br /><applet load="1xon" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1xon" size=" | |||
caption="1xon, resolution 1.72Å" /> | caption="1xon, resolution 1.72Å" /> | ||
'''Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Piclamilast'''<br /> | '''Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Piclamilast'''<br /> | ||
==Overview== | ==Overview== | ||
Phosphodiesterases (PDEs) comprise a large family of enzymes that catalyze | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1XON 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, MG, PIL, B3P and EDO 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:// | 1XON 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>, <scene name='pdbligand=PIL:'>PIL</scene>, <scene name='pdbligand=B3P:'>B3P</scene> and <scene name='pdbligand=EDO:'>EDO</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=1XON OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Artis, D | [[Category: Artis, D R.]] | ||
[[Category: Bollag, G.]] | [[Category: Bollag, G.]] | ||
[[Category: Card, G | [[Category: Card, G L.]] | ||
[[Category: England, B | [[Category: England, B P.]] | ||
[[Category: Fong, D.]] | [[Category: Fong, D.]] | ||
[[Category: Gillette, S.]] | [[Category: Gillette, S.]] | ||
[[Category: Ibrahim, P | [[Category: Ibrahim, P N.]] | ||
[[Category: Kim, S | [[Category: Kim, S H.]] | ||
[[Category: Lee, B.]] | [[Category: Lee, B.]] | ||
[[Category: Luu, C.]] | [[Category: Luu, C.]] | ||
[[Category: Milburn, M | [[Category: Milburn, M V.]] | ||
[[Category: Powell, B.]] | [[Category: Powell, B.]] | ||
[[Category: Schlessinger, J.]] | [[Category: Schlessinger, J.]] | ||
[[Category: Suzuki, Y.]] | [[Category: Suzuki, Y.]] | ||
[[Category: Tabrizizad, M.]] | [[Category: Tabrizizad, M.]] | ||
[[Category: Zhang, K | [[Category: Zhang, K Y.J.]] | ||
[[Category: B3P]] | [[Category: B3P]] | ||
[[Category: EDO]] | [[Category: EDO]] | ||
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[[Category: piclamilast]] | [[Category: piclamilast]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:56:59 2008'' | ||
