1ror
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CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH AMP
OverviewOverview
Phosphodiesterase catalyzes the hydrolysis of the intracellular second, messenger 3',5'-cyclic AMP (cAMP) into the corresponding 5'-nucleotide., Phosphodiesterase 4 (PDE4), the major cAMP-specific PDE in inflammatory, and immune cells, is an attractive target for the treatment of asthma and, COPD. We have determined crystal structures of the catalytic domain of, PDE4B complexed with AMP (2.0 A), 8-Br-AMP (2.13 A) and the potent, inhibitor rolipram (2.0 A). All the ligands bind in the same hydrophobic, pocket and can interact directly with the active site metal ions. The, identity of these metal ions was examined using X-ray anomalous difference, data. The structure of the AMP complex confirms the location of the, catalytic site and allowed us to speculate about the detailed mechanism of, catalysis. The high-resolution structures provided the experimental, insight into the nucleotide selectivity of phosphodiesterase. 8-Br-AMP, binds in the syn conformation to the enzyme and demonstrates an, alternative nucleotide-binding mode. Rolipram occupies much of the, AMP-binding site and forms two hydrogen bonds with Gln443 similar to the, nucleotides.
About this StructureAbout this Structure
1ROR is a Single protein structure of sequence from Homo sapiens with ZN and AMP as ligands. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram., Xu RX, Rocque WJ, Lambert MH, Vanderwall DE, Luther MA, Nolte RT, J Mol Biol. 2004 Mar 19;337(2):355-65. PMID:15003452
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