1xp0: Difference between revisions

Revision as of 15:19, 3 May 2008

Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil

OverviewOverview

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 StructureAbout this Structure

1XP0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Sat May 3 15:19:06 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1xp0.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1xp0 |SIZE=350|CAPTION= <scene name='initialview01'>1xp0</scene>, resolution 1.79&Aring;
+The line below this paragraph, containing "STRUCTURE_1xp0", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VDN:2-{2-ETHOXY-5-[(4-ETHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}-5-METHYL-7-PROPYLIMIDAZO[5,1-F][1,2,4]TRIAZIN-4(1H)-ONE'>VDN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE= PDE5A, PDE5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1xp0|  PDB=1xp0  |  SCENE=  }}
-|RELATEDENTRY=[[1xlx|1XLX]], [[1xlz|1XLZ]], [[1xm4|1XM4]], [[1xm6|1XM6]], [[1xmu|1XMU]], [[1xmy|1XMY]], [[1xn0|1XN0]], [[1xom|1XOM]], [[1xon|1XON]], [[1xoq|1XOQ]], [[1xor|1XOR]], [[1xos|1XOS]], [[1xot|1XOT]], [[1xoz|1XOZ]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xp0 OCA], [http://www.ebi.ac.uk/pdbsum/1xp0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xp0 RCSB]</span>
-}}
 '''Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil'''
@@ Line 42: / Line 39: @@
 [[Category: Tabrizizad, M.]]
 [[Category: Zhang, K Y.J.]]
-[[Category: levitra]]
+[[Category: Levitra]]
-[[Category: pde]]
+[[Category: Pde]]
-[[Category: pde5a]]
+[[Category: Pde5a]]
-[[Category: phosphodiesterase]]
+[[Category: Phosphodiesterase]]
-[[Category: vardenafil]]
+[[Category: Vardenafil]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 15:19:06 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:52:39 2008''