5obk: Difference between revisions
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==The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-(hydroxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one== | ==The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-(hydroxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one== | ||
<StructureSection load='5obk' size='340' side='right' caption='[[5obk]], [[Resolution|resolution]] 1.00Å' scene=''> | <StructureSection load='5obk' size='340' side='right'caption='[[5obk]], [[Resolution|resolution]] 1.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5obk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OBK OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5obk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OBK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OBK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9QN:(1~{S},5~{S},6~{R})-10-[3,5-bis(chloranyl)phenyl]sulfonyl-5-(hydroxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one'>9QN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9QN:(1~{S},5~{S},6~{R})-10-[3,5-bis(chloranyl)phenyl]sulfonyl-5-(hydroxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one'>9QN</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5obk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5obk OCA], [http://pdbe.org/5obk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5obk RCSB], [http://www.ebi.ac.uk/pdbsum/5obk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5obk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5obk" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5obk" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[FKBP 3D structures|FKBP 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Peptidylprolyl isomerase]] | [[Category: Peptidylprolyl isomerase]] | ||
[[Category: Bracher, A]] | [[Category: Bracher, A]] | ||
Revision as of 15:20, 26 August 2020
The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-(hydroxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-oneThe Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-((3,5-dichlorophenyl)sulfonyl)-5-(hydroxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one
Structural highlights
Function[FKBP5_HUMAN] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP. Publication Abstract from PubMedFK506-binding proteins (FKBPs) are evolutionary conserved proteins that display peptidyl-prolyl isomerase activity and act as co-receptors for immunosuppressants. Microbial macrophage infectivity potentiator (Mip) type FKBPs can enhance infectivity. However, developing drug-like ligands for FKBPs or Mips has proven difficult and many FKBPs/Mips still lack a biologically useful ligand. To explore the scope and potential of C5-substituted-[4.3.1]-aza-bicyclic sulfonamides as a broadly applicable class of FKBP inhibitors, we developed a new synthesis for the bicyclic core scaffold and used it to prepare a FKBP/Mip-focused library. This allowed a systematic structure-activity relationship analysis across key human FKBPs and microbial Mips, yielding highly improved inhibitors for all FKBPs studied. A co-crystal structure confirmed the molecular binding mode of the core structure and explained the affinity gain by preferred substitutents. The best FKBP/Mip ligands showed promising anti-malarial, anti-leginonella and anti-clamydial properties in cellular models of infectivity, suggesting substituted-[4.3.1]-aza-bicyclic sulfonamides as a novel class of anti-infectives. Chemogenomic profiling of human and microbial FK506-binding proteins.,Pomplun S, Sippel C, Hahle A, Tay D, Shima K, Klages A, Unal CM, Riess B, Toh HT, Hansen G, Yoon HS, Bracher A, Preiser PR, Rupp J, Steinert M, Hausch F J Med Chem. 2018 Mar 26. doi: 10.1021/acs.jmedchem.8b00137. PMID:29578710[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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