1ro9
From Proteopedia
(New page: 200px<br /> <applet load="1ro9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ro9, resolution 2.13Å" /> '''CRYSTAL STRUCTURES ...) |
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| - | [[Image:1ro9.gif|left|200px]]<br /> | + | [[Image:1ro9.gif|left|200px]]<br /><applet load="1ro9" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ro9" size=" | + | |
caption="1ro9, resolution 2.13Å" /> | caption="1ro9, resolution 2.13Å" /> | ||
'''CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP'''<br /> | '''CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Phosphodiesterase catalyzes the hydrolysis of the intracellular second | + | 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 Structure== | ==About this Structure== | ||
| - | 1RO9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and 8BR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1RO9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=8BR:'>8BR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RO9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Lambert, M | + | [[Category: Lambert, M H.]] |
| - | [[Category: Nolte, R | + | [[Category: Nolte, R T.]] |
| - | [[Category: Rocque, W | + | [[Category: Rocque, W J.]] |
| - | [[Category: Vanderwall, D | + | [[Category: Vanderwall, D E.]] |
| - | [[Category: Xu, R | + | [[Category: Xu, R X.]] |
[[Category: 8BR]] | [[Category: 8BR]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: pde]] | [[Category: pde]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:52:53 2008'' |
Revision as of 12:52, 21 February 2008
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CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP
Overview
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 Structure
1RO9 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
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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