3sl3

From Proteopedia

(Difference between revisions)

Revision as of 07:52, 5 August 2016

Crystal structure of the apo form of the catalytic domain of PDE4D2

Structural highlights

3sl3 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:	, , , , ,
Related:	1ptw, 3sl4, 3sl5, 3sl6, 3sl8
Gene:	DPDE3, PDE4D (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]

Publication Abstract from PubMed

PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor.

Thiophene inhibitors of PDE4: Crystal structures show a second binding mode at the catalytic domain of PDE4D2.,Nankervis JL, Feil SC, Hancock NC, Zheng Z, Ng HL, Morton CJ, Holien JK, Ho PW, Frazzetto MM, Jennings IG, Manallack DT, Martin TJ, Thompson PE, Parker MW Bioorg Med Chem Lett. 2011 Dec 1;21(23):7089-93. Epub 2011 Oct 5. PMID:22030030^[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
↑ Nankervis JL, Feil SC, Hancock NC, Zheng Z, Ng HL, Morton CJ, Holien JK, Ho PW, Frazzetto MM, Jennings IG, Manallack DT, Martin TJ, Thompson PE, Parker MW. Thiophene inhibitors of PDE4: Crystal structures show a second binding mode at the catalytic domain of PDE4D2. Bioorg Med Chem Lett. 2011 Dec 1;21(23):7089-93. Epub 2011 Oct 5. PMID:22030030 doi:10.1016/j.bmcl.2011.09.109

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3sl3"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the apo form of the catalytic domain of PDE4D2==
 <StructureSection load='3sl3' size='340' side='right' caption='[[3sl3]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3sl3]] is a 4 chain structure with 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=3SL3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SL3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3sl3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SL3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SL3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ptw|1ptw]], [[3sl4|3sl4]], [[3sl5|3sl5]], [[3sl6|3sl6]], [[3sl8|3sl8]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DPDE3, PDE4D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DPDE3, PDE4D ([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=3sl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sl3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sl3 RCSB], [http://www.ebi.ac.uk/pdbsum/3sl3 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=3sl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sl3 OCA], [http://pdbe.org/3sl3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sl3 RCSB], [http://www.ebi.ac.uk/pdbsum/3sl3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sl3 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3sl3" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 29: / Line 31: @@
 </StructureSection>
 [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Feil, S F]]
 [[Category: Camp hydrolysis]]
 [[Category: Catalytic mechanism]]
 [[Category: Hydrolase]]

3sl3

From Proteopedia

Revision as of 07:52, 5 August 2016

Crystal structure of the apo form of the catalytic domain of PDE4D2

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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