2h44
From Proteopedia
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Crystal structure of PDE5A1 in complex with icarisid II
Overview
Phosphodiesterase-5 (PDE5) is the target for sildenafil, vardenafil, and, tadalafil, which are drugs for treatment of erectile dysfunction and, pulmonary hypertension. We report here the crystal structures of a fully, active catalytic domain of unliganded PDE5A1 and its complexes with, sildenafil or icarisid II. These structures together with the, PDE5A1-isobutyl-1-methylxanthine complex show that the H-loop (residues, 660-683) at the active site of PDE5A1 has four different conformations and, migrates 7-35A upon inhibitor binding. In addition, the conformation of, sildenafil reported herein differs significantly from those in the, previous structures of chimerically hybridized or almost inactive PDE5., Mutagenesis and kinetic analyses confirm that the H-loop is particularly, important for substrate recognition and that invariant Gly(659), which, immediately precedes the H-loop, is critical for optimal substrate, affinity and catalytic activity.
About this Structure
2H44 is a Single protein structure of sequence from Homo sapiens with ZN, MG and 7CA as ligands. Active as 3',5'-cyclic-GMP phosphodiesterase, with EC number 3.1.4.35 Full crystallographic information is available from OCA.
Reference
Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development., Wang H, Liu Y, Huai Q, Cai J, Zoraghi R, Francis SH, Corbin JD, Robinson H, Xin Z, Lin G, Ke H, J Biol Chem. 2006 Jul 28;281(30):21469-79. Epub 2006 May 30. PMID:16735511
Page seeded by OCA on Mon Nov 12 22:26:01 2007
Categories: 3',5'-cyclic-GMP phosphodiesterase | Homo sapiens | Single protein | Ke, H. | Wang, H. | 7CA | MG | ZN | Flavonoid | Icarisid ii | Pde5a inhibitor
