2wxg: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==THE CRYSTAL STRUCTURE OF THE MURINE CLASS IA PI 3-KINASE P110DELTA IN COMPLEX WITH SW13.== | ==THE CRYSTAL STRUCTURE OF THE MURINE CLASS IA PI 3-KINASE P110DELTA IN COMPLEX WITH SW13.== | ||
<StructureSection load='2wxg' size='340' side='right' caption='[[2wxg]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='2wxg' size='340' side='right' caption='[[2wxg]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wxg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2wxg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WXG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WXG FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZZN:2-{[4-AMINO-3-(3-FLUORO-5-HYDROXYPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL]METHYL}-5-METHYL-3-(2-METHYLPHENYL)QUINAZOLIN-4(3H)-ONE'>ZZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZZN:2-{[4-AMINO-3-(3-FLUORO-5-HYDROXYPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL]METHYL}-5-METHYL-3-(2-METHYLPHENYL)QUINAZOLIN-4(3H)-ONE'>ZZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wxm|2wxm]], [[2wxh|2wxh]], [[2wxk|2wxk]], [[2wxl|2wxl]], [[2wxi|2wxi]], [[2wxp|2wxp]], [[2wxo|2wxo]], [[2wxf|2wxf]], [[2wxq|2wxq]], [[2wxn|2wxn]], [[2wxe|2wxe]], [[2wxj|2wxj]], [[2wxr|2wxr]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wxm|2wxm]], [[2wxh|2wxh]], [[2wxk|2wxk]], [[2wxl|2wxl]], [[2wxi|2wxi]], [[2wxp|2wxp]], [[2wxo|2wxo]], [[2wxf|2wxf]], [[2wxq|2wxq]], [[2wxn|2wxn]], [[2wxe|2wxe]], [[2wxj|2wxj]], [[2wxr|2wxr]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </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=2wxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wxg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wxg RCSB], [http://www.ebi.ac.uk/pdbsum/2wxg 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=2wxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wxg OCA], [http://pdbe.org/2wxg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wxg RCSB], [http://www.ebi.ac.uk/pdbsum/2wxg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wxg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
| Line 16: | Line 17: | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=2wxg ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 26: | Line 27: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2wxg" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
| Line 33: | Line 35: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Lk3 transgenic mice]] | ||
[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]] | [[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]] | ||
[[Category: Berndt, A]] | [[Category: Berndt, A]] | ||
Revision as of 00:03, 12 August 2016
THE CRYSTAL STRUCTURE OF THE MURINE CLASS IA PI 3-KINASE P110DELTA IN COMPLEX WITH SW13.THE CRYSTAL STRUCTURE OF THE MURINE CLASS IA PI 3-KINASE P110DELTA IN COMPLEX WITH SW13.
Structural highlights
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 PubMedDeregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies. The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.,Berndt A, Miller S, Williams O, Le DD, Houseman BT, Pacold JI, Gorrec F, Hon WC, Liu Y, Rommel C, Gaillard P, Ruckle T, Schwarz MK, Shokat KM, Shaw JP, Williams RL Nat Chem Biol. 2010 Feb;6(2):117-24. PMID:20081827[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||