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spinqualitylabelsall models 1rkp, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of PDE5A1-IBMX

Overview

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes, controlling cellular concentrations of the second messengers cAMP and, cGMP. Crystal structures of the catalytic domains of cGMP-specific PDE5A1, and cAMP-specific PDE4D2 in complex with the nonselective inhibitor, 3-isobutyl-1-methylxanthine have been determined at medium resolution. The, catalytic domain of PDE5A1 has the same topological folding as that of, PDE4D2, but three regions show different tertiary structures, including, residues 79-113, 208-224 (H-loop), and 341-364 (M-loop) in PDE4D2 or, 535-566, 661-676, and 787-812 in PDE5A1, respectively. Because H- and, M-loops are involved in binding of the selective inhibitors, the different, conformations of the loops, thus the distinct shapes of the active sites, will be a determinant of inhibitor selectivity in PDEs. IBMX binds to a, subpocket that comprises key residues Ile-336, Phe-340, Gln-369, and, Phe-372 of PDE4D2 or Val-782, Phe-786, Gln-817, and Phe-820 of PDE5A1., This subpocket may be a common site for binding nonselective inhibitors of, PDEs.

About this Structure

1RKP is a Single protein structure of sequence from Homo sapiens with ZN, MG and IBM as ligands. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Full crystallographic information is available from OCA.

Reference

Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivity., Huai Q, Liu Y, Francis SH, Corbin JD, Ke H, J Biol Chem. 2004 Mar 26;279(13):13095-101. Epub 2003 Dec 10. PMID:14668322

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