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1ro9

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CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP

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Retrieved from "http://52.214.119.220/wiki/index.php/1ro9"

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-[[Image:1ro9.gif|left|200px]]
- {{Structure
+==CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP==
-|PDB= 1ro9 |SIZE=350|CAPTION= <scene name='initialview01'>1ro9</scene>, resolution 2.13&Aring;
+<StructureSection load='1ro9' size='340' side='right'caption='[[1ro9]], [[Resolution|resolution]] 2.13&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=8BR:8-BROMO-ADENOSINE-5&#39;-MONOPHOSPHATE'>8BR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+<table><tr><td colspan='2'>[[1ro9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RO9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RO9 FirstGlance]. <br>
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.13&#8491;</td></tr>
-|GENE= PDE4B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8BR:8-BROMO-ADENOSINE-5-MONOPHOSPHATE'>8BR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-|DOMAIN=
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ro9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ro9 OCA], [https://pdbe.org/1ro9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ro9 RCSB], [https://www.ebi.ac.uk/pdbsum/1ro9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ro9 ProSAT]</span></td></tr>
-|RELATEDENTRY=[[1ro6|1RO6]]
+</table>
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ro9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ro9 OCA], [http://www.ebi.ac.uk/pdbsum/1ro9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ro9 RCSB]</span>
+== Function ==
-}}
+[https://www.uniprot.org/uniprot/PDE4B_HUMAN PDE4B_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.<ref>PMID:10846163</ref> <ref>PMID:15003452</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ro/1ro9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ro9 ConSurf].
+<div style="clear:both"></div>
-'''CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP'''
+==See Also==
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
+== References ==
-==Overview==
+<references/>
-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.
+__TOC__
+</StructureSection>
-==About this Structure==
-RO9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RO9 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:[http://www.ncbi.nlm.nih.gov/pubmed/15003452 15003452]
-[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Lambert, M H.]]
+[[Category: Lambert MH]]
-[[Category: Nolte, R T.]]
+[[Category: Nolte RT]]
-[[Category: Rocque, W J.]]
+[[Category: Rocque WJ]]
-[[Category: Vanderwall, D E.]]
+[[Category: Vanderwall DE]]
-[[Category: Xu, R X.]]
+[[Category: Xu RX]]
-[[Category: 8-br-amp]]
-[[Category: pde]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:30:46 2008''

1ro9

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CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP

Structural highlights

Function

Evolutionary Conservation

See Also

References

Contents

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