1xor
From Proteopedia
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|PDB= 1xor |SIZE=350|CAPTION= <scene name='initialview01'>1xor</scene>, resolution 1.54Å | |PDB= 1xor |SIZE=350|CAPTION= <scene name='initialview01'>1xor</scene>, resolution 1.54Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZAR:6-(4-DIFLUOROMETHOXY-3-METHOXY-PHENYL)-2H-PYRIDAZIN-3-ONE'>ZAR</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= 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]], [[1xon|1XON]], [[1xoq|1XOQ]], [[1xos|1XOS]], [[1xot|1XOT]], [[1xoz|1XOZ]], [[1xp0|1XP0]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xor OCA], [http://www.ebi.ac.uk/pdbsum/1xor PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xor 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. | ||
| - | |||
| - | ==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: Tabrizizad, M.]] | [[Category: Tabrizizad, M.]] | ||
[[Category: Zhang, K Y.J.]] | [[Category: Zhang, K Y.J.]] | ||
| - | [[Category: MG]] | ||
| - | [[Category: ZAR]] | ||
| - | [[Category: ZN]] | ||
[[Category: pde]] | [[Category: pde]] | ||
[[Category: pde4d]] | [[Category: pde4d]] | ||
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[[Category: zardaverine]] | [[Category: zardaverine]] | ||
| - | ''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 00:52:32 2008'' |
Revision as of 21:52, 30 March 2008
| |||||||
| , resolution 1.54Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | PDE4D (Homo sapiens) | ||||||
| Activity: | 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 | ||||||
| Related: | 1XLX, 1XLZ, 1XM4, 1XM6, 1XMU, 1XMY, 1XN0, 1XOM, 1XON, 1XOQ, 1XOS, 1XOT, 1XOZ, 1XP0
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Zardaverine
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.
About this Structure
1XOR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for the activity of drugs that inhibit phosphodiesterases., Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY, Structure. 2004 Dec;12(12):2233-47. PMID:15576036
Page seeded by OCA on Mon Mar 31 00:52:32 2008
Categories: 3',5'-cyclic-nucleotide phosphodiesterase | Homo sapiens | Single protein | Artis, D R. | Bollag, G. | Card, G L. | England, B P. | Fong, D. | Gillette, S. | Ibrahim, P N. | Kim, S H. | Lee, B. | Luu, C. | Milburn, M V. | Powell, B. | Schlessinger, J. | Suzuki, Y. | Tabrizizad, M. | Zhang, K Y.J. | Pde | Pde4d | Phosphodiesterase | Zardaverine
