3hdz

From Proteopedia

(Difference between revisions)

Current revision

Identification, Synthesis, and SAR of Amino Substituted Pyrido[3,2b]pryaziones as Potent and Selective PDE5 Inhibitors

Structural highlights

3hdz is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDE5A_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.PDE4A_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.^[1] ^[2]

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

A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which show potent inhibition of the PDE5 enzyme. Synthetic details and some structure-activity relationships are also presented.

Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors.,Owen DR, Walker JK, Jon Jacobsen E, Freskos JN, Hughes RO, Brown DL, Bell AS, Brown DG, Phillips C, Mischke BV, Molyneaux JM, Fobian YM, Heasley SE, Moon JB, Stallings WC, Joseph Rogier D, Fox DN, Palmer MJ, Ringer T, Rodriquez-Lens M, Cubbage JW, Blevis-Bal RM, Benson AG, Acker BA, Maddux TM, Tollefson MB, Bond BR, Macinnes A, Yu Y Bioorg Med Chem Lett. 2009 Aug 1;19(15):4088-91. Epub 2009 Jun 6. PMID:19540112^[3]

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

References

↑ Lario PI, Bobechko B, Bateman K, Kelly J, Vrielink A, Huang Z. Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells. Arch Biochem Biophys. 2001 Oct 1;394(1):54-60. PMID:11566027 doi:http://dx.doi.org/10.1006/abbi.2001.2513
↑ Wang H, Peng MS, Chen Y, Geng J, Robinson H, Houslay MD, Cai J, Ke H. Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. Biochem J. 2007 Dec 1;408(2):193-201. PMID:17727341 doi:http://dx.doi.org/10.1042/BJ20070970
↑ Owen DR, Walker JK, Jon Jacobsen E, Freskos JN, Hughes RO, Brown DL, Bell AS, Brown DG, Phillips C, Mischke BV, Molyneaux JM, Fobian YM, Heasley SE, Moon JB, Stallings WC, Joseph Rogier D, Fox DN, Palmer MJ, Ringer T, Rodriquez-Lens M, Cubbage JW, Blevis-Bal RM, Benson AG, Acker BA, Maddux TM, Tollefson MB, Bond BR, Macinnes A, Yu Y. Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4088-91. Epub 2009 Jun 6. PMID:19540112 doi:10.1016/j.bmcl.2009.06.012

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/3hdz"

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:3hdz.jpg|left|200px]]
-<!--
+==Identification, Synthesis, and SAR of Amino Substituted Pyrido[3,2b]pryaziones as Potent and Selective PDE5 Inhibitors==
-The line below this paragraph, containing "STRUCTURE_3hdz", creates the "Structure Box" on the page.
+<StructureSection load='3hdz' size='340' side='right'caption='[[3hdz]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3hdz]] is a 1 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=3HDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HDZ FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PD6:5-AMINO-1-BUTYL-7-PHENYL-1,6-NAPHTHYRIDIN-4(1H)-ONE'>PD6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3hdz|  PDB=3hdz  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hdz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdz OCA], [https://pdbe.org/3hdz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hdz RCSB], [https://www.ebi.ac.uk/pdbsum/3hdz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hdz ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PDE5A_HUMAN PDE5A_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.[https://www.uniprot.org/uniprot/PDE4A_HUMAN PDE4A_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:11566027</ref> <ref>PMID:17727341</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/hd/3hdz_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=3hdz ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which show potent inhibition of the PDE5 enzyme. Synthetic details and some structure-activity relationships are also presented.
-===Identification, Synthesis, and SAR of Amino Substituted Pyrido[3,2b]pryaziones as Potent and Selective PDE5 Inhibitors===
+Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors.,Owen DR, Walker JK, Jon Jacobsen E, Freskos JN, Hughes RO, Brown DL, Bell AS, Brown DG, Phillips C, Mischke BV, Molyneaux JM, Fobian YM, Heasley SE, Moon JB, Stallings WC, Joseph Rogier D, Fox DN, Palmer MJ, Ringer T, Rodriquez-Lens M, Cubbage JW, Blevis-Bal RM, Benson AG, Acker BA, Maddux TM, Tollefson MB, Bond BR, Macinnes A, Yu Y Bioorg Med Chem Lett. 2009 Aug 1;19(15):4088-91. Epub 2009 Jun 6. PMID:19540112<ref>PMID:19540112</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3hdz" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19540112}}, adds the Publication Abstract to the page
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19540112 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19540112}}
+__TOC__
+</StructureSection>
-==About this Structure==
-HDZ is a 1 chain 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=3HDZ OCA].
-==Reference==
-<ref group="xtra">PMID:19540112</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Brown, D G.]]
+[[Category: Large Structures]]
-[[Category: Cubbage, J W.]]
+[[Category: Brown DG]]
-[[Category: Hughes, R O.]]
+[[Category: Cubbage JW]]
-[[Category: Jacobsen, E J.]]
+[[Category: Hughes RO]]
-[[Category: Walker, J K.]]
+[[Category: Jacobsen EJ]]
-[[Category: Alternative splicing]]
+[[Category: Walker JK]]
-[[Category: Camp]]
-[[Category: Cgmp]]
-[[Category: Cgmp-binding]]
-[[Category: Hydrolase]]
-[[Category: Inhibition]]
-[[Category: Magnesium]]
-[[Category: Metal-binding]]
-[[Category: Nucleotide-binding]]
-[[Category: Pde-5]]
-[[Category: Pde5]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism allosteric enzyme]]
-[[Category: Zinc]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul  8 09:28:05 2009''

3hdz

From Proteopedia

Current revision

Identification, Synthesis, and SAR of Amino Substituted Pyrido[3,2b]pryaziones as Potent and Selective PDE5 Inhibitors

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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