1xp0

From Proteopedia

Revision as of 15:10, 15 February 2008

Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil

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

1XP0 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 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

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