3hmv
From Proteopedia
(Difference between revisions)
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<StructureSection load='3hmv' size='340' side='right'caption='[[3hmv]], [[Resolution|resolution]] 2.23Å' scene=''> | <StructureSection load='3hmv' size='340' side='right'caption='[[3hmv]], [[Resolution|resolution]] 2.23Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3hmv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[3hmv]] 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=3HMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HMV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HBT:(6S)-6-METHYL-2-{[(2-NITROPHENYL)CARBONYL]AMINO}-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDE'>HBT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.23Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HBT:(6S)-6-METHYL-2-{[(2-NITROPHENYL)CARBONYL]AMINO}-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDE'>HBT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmv OCA], [https://pdbe.org/3hmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hmv RCSB], [https://www.ebi.ac.uk/pdbsum/3hmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hmv ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmv OCA], [https://pdbe.org/3hmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hmv RCSB], [https://www.ebi.ac.uk/pdbsum/3hmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hmv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</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=3hmv ConSurf]. | </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=3hmv ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | A PDE4B over 4D-selective inhibitor programme was initiated to capitalise on the recently discovered predominance of the PDE4B subtype in inflammatory cell regulation. The SAR of a tetrahydrobenzothiophene (THBT) series did not agree with either of two proposed docking modes in the 4B binding site. A subsequent X-ray co-crystal structure determination revealed that the THBT ligand displaces the Gln-443 residue, invariably ligand-anchoring in previous PDE4 co-crystal structures, and even shifts helix-15 by 1-2A. For the first time, several residues of the C-terminus previously proposed to be involved in subtype selectivity are resolved and three of them extend into the ligand binding site potentially allowing for selective drug design. | ||
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| - | Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode.,Kranz M, Wall M, Evans B, Miah A, Ballantine S, Delves C, Dombroski B, Gross J, Schneck J, Villa JP, Neu M, Somers DO Bioorg Med Chem. 2009 Jul 15;17(14):5336-41. Epub 2009 Apr 5. PMID:19525117<ref>PMID:19525117</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3hmv" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
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[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Neu | + | [[Category: Neu M]] |
| - | [[Category: Somers | + | [[Category: Somers DO]] |
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Current revision
Catalytic domain of human phosphodiesterase 4B2B in complex with a tetrahydrobenzothiophene inhibitor
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