1q9m
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Selective inhibitors against the 11 families of cyclic nucleotide | + | Selective inhibitors against the 11 families of cyclic nucleotide phosphodiesterases (PDEs) are used to treat various human diseases. How the inhibitors selectively bind the conserved PDE catalytic domains is unknown. The crystal structures of the PDE4D2 catalytic domain in complex with (R)- or (R,S)-rolipram suggest that inhibitor selectivity is determined by the chemical nature of amino acids and subtle conformational changes of the binding pockets. The conformational states of Gln369 in PDE4D2 may play a key role in inhibitor recognition. The corresponding Y329S mutation in PDE7 may lead to loss of the hydrogen bonds between rolipram and Gln369 and is thus a possible reason explaining PDE7's insensitivity to rolipram inhibition. Docking of the PDE5 inhibitor sildenafil into the PDE4 catalytic pocket further helps understand inhibitor selectivity. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Q9M 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=ROL:'>ROL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 1Q9M 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=ROL:'>ROL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1OYM. 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=1Q9M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Huai, Q.]] | [[Category: Huai, Q.]] | ||
[[Category: Ke, H.]] | [[Category: Ke, H.]] | ||
| - | [[Category: Kim, H | + | [[Category: Kim, H Y.]] |
[[Category: Liu, Y.]] | [[Category: Liu, Y.]] | ||
[[Category: Sun, Y.]] | [[Category: Sun, Y.]] | ||
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[[Category: specific inhibitor]] | [[Category: specific inhibitor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:37:21 2008'' |
Revision as of 12:37, 21 February 2008
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Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity
Contents |
Overview
Selective inhibitors against the 11 families of cyclic nucleotide phosphodiesterases (PDEs) are used to treat various human diseases. How the inhibitors selectively bind the conserved PDE catalytic domains is unknown. The crystal structures of the PDE4D2 catalytic domain in complex with (R)- or (R,S)-rolipram suggest that inhibitor selectivity is determined by the chemical nature of amino acids and subtle conformational changes of the binding pockets. The conformational states of Gln369 in PDE4D2 may play a key role in inhibitor recognition. The corresponding Y329S mutation in PDE7 may lead to loss of the hydrogen bonds between rolipram and Gln369 and is thus a possible reason explaining PDE7's insensitivity to rolipram inhibition. Docking of the PDE5 inhibitor sildenafil into the PDE4 catalytic pocket further helps understand inhibitor selectivity.
Disease
Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[600129]
About this Structure
1Q9M is a Single protein structure of sequence from Homo sapiens with and as ligands. This structure supersedes the now removed PDB entry 1OYM. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Full crystallographic information is available from OCA.
Reference
Three-dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity., Huai Q, Wang H, Sun Y, Kim HY, Liu Y, Ke H, Structure. 2003 Jul;11(7):865-73. PMID:12842049
Page seeded by OCA on Thu Feb 21 14:37:21 2008
Categories: 3',5'-cyclic-nucleotide phosphodiesterase | Homo sapiens | Single protein | Huai, Q. | Ke, H. | Kim, H Y. | Liu, Y. | Sun, Y. | Wang, H. | ROL | ZN | Pde | Rolipram | Specific inhibitor
