1oyn
From Proteopedia
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|PDB= 1oyn |SIZE=350|CAPTION= <scene name='initialview01'>1oyn</scene>, resolution 2.0Å | |PDB= 1oyn |SIZE=350|CAPTION= <scene name='initialview01'>1oyn</scene>, resolution 2.0Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ROL:ROLIPRAM'>ROL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= PDE4D2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PDE4D2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1oym|1OYM]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1oyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oyn OCA], [http://www.ebi.ac.uk/pdbsum/1oyn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1oyn RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600129 600129]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sun, Y.]] | [[Category: Sun, Y.]] | ||
[[Category: Wang, H.]] | [[Category: Wang, H.]] | ||
| - | [[Category: ROL]] | ||
| - | [[Category: ZN]] | ||
[[Category: camp]] | [[Category: camp]] | ||
[[Category: pde]] | [[Category: pde]] | ||
[[Category: rolipram]] | [[Category: rolipram]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:52:13 2008'' |
Revision as of 19:52, 30 March 2008
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| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | PDE4D2 (Homo sapiens) | ||||||
| Activity: | 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 | ||||||
| Related: | 1OYM
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of PDE4D2 in complex with (R,S)-rolipram
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.
About this Structure
1OYN is a Single protein structure of sequence from Homo sapiens. 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 Sun Mar 30 22:52:13 2008
Categories: 3',5'-cyclic-nucleotide phosphodiesterase | Homo sapiens | Single protein | Huai, Q. | Ke, H. | Kim, H Y. | Liu, Y. | Sun, Y. | Wang, H. | Camp | Pde | Rolipram
