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1ptw

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Revision as of 08:14, 24 February 2018

The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis

Structural highlights

1ptw is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	PDE4D2 (HUMAN)
Activity:	3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PDE4D_HUMAN] Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:614613]. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.^[1]

Function

[PDE4D_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Cyclic nucleotide phosphodiesterases (PDEs) regulate the intracellular concentrations of cyclic 3',5'-adenosine and guanosine monophosphates (cAMP and cGMP, respectively) by hydrolyzing them to AMP and GMP, respectively. Family-selective inhibitors of PDEs have been studied for treatment of various human diseases. However, the catalytic mechanism of cyclic nucleotide hydrolysis by PDEs has remained unclear. We determined the crystal structure of the human PDE4D2 catalytic domain in complex with AMP at 2.4 A resolution. In this structure, two divalent metal ions simultaneously interact with the phosphate group of AMP, implying a binuclear catalysis. In addition, the structure suggested that a hydroxide ion or a water bridging two metal ions may serve as the nucleophile for the hydrolysis of the cAMP phosphodiester bond.

The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis.,Huai Q, Colicelli J, Ke H Biochemistry. 2003 Nov 18;42(45):13220-6. PMID:14609333^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V. Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. Am J Hum Genet. 2012 Apr 6;90(4):740-5. doi: 10.1016/j.ajhg.2012.03.003. Epub, 2012 Mar 29. PMID:22464250 doi:10.1016/j.ajhg.2012.03.003
↑ Zhang KY, Card GL, Suzuki Y, Artis DR, Fong D, Gillette S, Hsieh D, Neiman J, West BL, Zhang C, Milburn MV, Kim SH, Schlessinger J, Bollag G. A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell. 2004 Jul 23;15(2):279-86. PMID:15260978 doi:http://dx.doi.org/10.1016/j.molcel.2004.07.005
↑ Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY. Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004 Dec;12(12):2233-47. PMID:15576036 doi:http://dx.doi.org/10.1016/j.str.2004.10.004
↑ Huai Q, Colicelli J, Ke H. The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis. Biochemistry. 2003 Nov 18;42(45):13220-6. PMID:14609333 doi:10.1021/bi034653e

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis==
 <StructureSection load='1ptw' size='340' side='right' caption='[[1ptw]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE4D2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ptw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ptw OCA], [http://pdbe.org/1ptw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ptw RCSB], [http://www.ebi.ac.uk/pdbsum/1ptw PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ptw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ptw OCA], [http://pdbe.org/1ptw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ptw RCSB], [http://www.ebi.ac.uk/pdbsum/1ptw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ptw ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pt/1ptw_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pt/1ptw_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 1ptw" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Phosphodiesterase|Phosphodiesterase]]
 == References ==
 <references/>

1ptw

From Proteopedia

Revision as of 08:14, 24 February 2018

The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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