1xon: Difference between revisions
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|PDB= 1xon |SIZE=350|CAPTION= <scene name='initialview01'>1xon</scene>, resolution 1.72Å | |PDB= 1xon |SIZE=350|CAPTION= <scene name='initialview01'>1xon</scene>, resolution 1.72Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PIL:3-(CYCLOPENTYLOXY)-N-(3,5-DICHLOROPYRIDIN-4-YL)-4-METHOXYBENZAMIDE'>PIL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|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= PDE4D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PDE4D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1xlx|1XLX]], [[1xlz|1XLZ]], [[1xm4|1XM4]], [[1xm6|1XM6]], [[1xmu|1XMU]], [[1xmy|1XMY]], [[1xn0|1XN0]], [[1xom|1XOM]], [[1xoq|1XOQ]], [[1xor|1XOR]], [[1xos|1XOS]], [[1xot|1XOT]], [[1xoz|1XOZ]], [[1xp0|1XP0]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xon OCA], [http://www.ebi.ac.uk/pdbsum/1xon PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xon RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Tabrizizad, M.]] | [[Category: Tabrizizad, M.]] | ||
[[Category: Zhang, K Y.J.]] | [[Category: Zhang, K Y.J.]] | ||
[[Category: pde]] | [[Category: pde]] | ||
[[Category: pde4d]] | [[Category: pde4d]] | ||
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[[Category: piclamilast]] | [[Category: piclamilast]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:52:29 2008'' | ||
