7apq - Revision history

OCA at 12:13, 1 February 2024

OCA — Thu, 01 Feb 2024 12:13:50 GMT

←Older revision		Revision as of 12:13, 1 February 2024
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	<StructureSection load='7apq' size='340' side='right'caption='[[7apq]], [[Resolution\|resolution]] 1.09Å' scene=''>		<StructureSection load='7apq' size='340' side='right'caption='[[7apq]], [[Resolution\|resolution]] 1.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7apq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7APQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7APQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7apq]] 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=7APQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7APQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RQW:(1~{S},5~{S},6~{R})-10-(1,3-benzothiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one'>RQW</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.09Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RQW:(1~{S},5~{S},6~{R})-10-(1,3-benzothiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one'>RQW</scene></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=7apq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7apq OCA], [https://pdbe.org/7apq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7apq RCSB], [https://www.ebi.ac.uk/pdbsum/7apq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7apq 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=7apq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7apq OCA], [https://pdbe.org/7apq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7apq RCSB], [https://www.ebi.ac.uk/pdbsum/7apq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7apq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/FKBP5_HUMAN FKBP5_HUMAN]] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.	+	[https://www.uniprot.org/uniprot/FKBP5_HUMAN FKBP5_HUMAN] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 7apq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7apq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[FKBP 3D structures\|FKBP 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Peptidylprolyl isomerase]]~~	+	[[Category: Bracher A]]
-	[[Category: Bracher, A]]	+	[[Category: Hausch F]]
-	[[Category: Hausch, F]]	+	[[Category: Kolos MJ]]
-	[[Category: Kolos~~, M J~~]]	+	[[Category: Krewald V]]
-	[[Category: Krewald, V]]	+	[[Category: Merz S]]
-	[[Category: Merz, S]]	+	[[Category: Meyners C]]
-	[[Category: Meyners, C]]	+	[[Category: Pomplun S]]
-	[[Category: Pomplun, S]]	+	[[Category: Purder P]]
-	[[Category: Purder, P]]	+	[[Category: Riess B]]
-	[[Category: Riess, B]]	+	[[Category: Voll MA]]
-	[[Category: Voll~~, M A]]~~	+
-	~~[[Category: Conformation analysis]]~~	+
-	~~[[Category: Density functional calculation]]~~	+
-	~~[[Category: Fkbp]]~~	+
-	~~[[Category: Isomerase]]~~	+
-	~~[[Category: Magic methyl~~]]	+

OCA at 10:02, 8 December 2021

OCA — Wed, 08 Dec 2021 10:02:56 GMT

←Older revision		Revision as of 10:02, 8 December 2021
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	==The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-(benzo[d]thiazol-6-ylsulfonyl)-5-(methoxymethyl)-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-(benzo[d]thiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one==
-	<StructureSection load='7apq' size='340' side='right'caption='[[7apq]]' scene=''>	+	<StructureSection load='7apq' size='340' side='right'caption='[[7apq]], [[Resolution\|resolution]] 1.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7APQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7APQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7apq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7APQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7APQ FirstGlance]. <br>
-	</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=7apq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7apq OCA], [https://pdbe.org/7apq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7apq RCSB], [https://www.ebi.ac.uk/pdbsum/7apq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7apq ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RQW:(1~{S},5~{S},6~{R})-10-(1,3-benzothiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one'>RQW</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7apq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7apq OCA], [https://pdbe.org/7apq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7apq RCSB], [https://www.ebi.ac.uk/pdbsum/7apq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7apq ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/FKBP5_HUMAN FKBP5_HUMAN]] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Methyl groups can have profound effects in drug discovery but the underlying mechanisms are diverse and incompletely understood. Here we report the stereospecific effect of a single, solvent-exposed methyl group in bicyclic [4.3.1] aza-amides, robustly leading to a 2 to 10-fold increase in binding affinity for FK506-binding proteins (FKBPs). This resulted in the most potent and efficient FKBP ligands known to date. By a combination of co-crystal structures, isothermal titration calorimetry (ITC), density-functional theory (DFT), and 3D reference interaction site model (3D-RISM) calculations we elucidated the origin of the observed affinity boost, which was purely entropically driven and relied on the displacement of a water molecule at the protein-ligand-bulk solvent interface. The best compounds potently occupied FKBPs in cells and enhanced bone morphogenic protein (BMP) signaling. Our results show how subtle manipulation of the solvent network can be used to design atom-efficient ligands for difficult, solvent-exposed binding pockets.
		+
		+	Picomolar FKBP inhibitors enabled by a single water-displacing methyl group in bicyclic [4.3.1] aza-amides.,Kolos JM, Pomplun S, Jung S, Riess B, Purder PL, Voll AM, Merz S, Gnatzy M, Geiger TM, Quist-Lokken I, Jatzlau J, Knaus P, Holien T, Bracher A, Meyners C, Czodrowski P, Krewald V, Hausch F Chem Sci. 2021 Nov 3;12(44):14758-14765. doi: 10.1039/d1sc04638a. eCollection, 2021 Nov 17. PMID:34820091<ref>PMID:34820091</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7apq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bracher A]]	+	[[Category: Peptidylprolyl isomerase]]
-	[[Category: Hausch F]]	+	[[Category: Bracher, A]]
-	[[Category: Kolos MJ]]	+	[[Category: Hausch, F]]
-	[[Category: Krewald V]]	+	[[Category: Kolos, M J]]
-	[[Category: Merz S]]	+	[[Category: Krewald, V]]
-	[[Category: Meyners C]]	+	[[Category: Merz, S]]
-	[[Category: Pomplun S]]	+	[[Category: Meyners, C]]
-	[[Category: Purder P]]	+	[[Category: Pomplun, S]]
-	[[Category: Riess B]]	+	[[Category: Purder, P]]
-	[[Category: Voll MA]]	+	[[Category: Riess, B]]
		+	[[Category: Voll, M A]]
		+	[[Category: Conformation analysis]]
		+	[[Category: Density functional calculation]]
		+	[[Category: Fkbp]]
		+	[[Category: Isomerase]]
		+	[[Category: Magic methyl]]

OCA at 06:13, 10 November 2021

OCA — Wed, 10 Nov 2021 06:13:30 GMT

←Older revision		Revision as of 06:13, 10 November 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7apq is ON HOLD until Paper Publication~~	+	==The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-(benzo[d]thiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one==
-		+	<StructureSection load='7apq' size='340' side='right'caption='[[7apq]]' scene=''>
-	~~Authors: Kolos, M.J., Pomplun, S., Riess, B., Purder, P., Voll, M.A., Merz, S., Bracher, A., Meyners, C., Krewald, V., Hausch, F.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7APQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7APQ FirstGlance]. <br>
-	~~Description:~~ The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-(benzo[d]thiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one	+	</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=7apq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7apq OCA], [https://pdbe.org/7apq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7apq RCSB], [https://www.ebi.ac.uk/pdbsum/7apq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7apq ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Krewald, V~~]]	+	__TOC__
-	[[Category: ~~Voll, M.A~~]]	+	</StructureSection>
-	[[Category: ~~Merz, S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Purder, P~~]]	+	[[Category: Bracher A]]
-	[[Category: ~~Pomplun,~~ S]]	+	[[Category: Hausch F]]
-	[[Category: Meyners, C]]	+	[[Category: Kolos MJ]]
-	[[Category: ~~Hausch, F~~]]	+	[[Category: Krewald V]]
-	[[Category: ~~Kolos, M.J~~]]	+	[[Category: Merz S]]
-	[[Category: ~~Bracher, A~~]]	+	[[Category: Meyners C]]
-	[[Category: ~~Riess, B~~]]	+	[[Category: Pomplun S]]
		+	[[Category: Purder P]]
		+	[[Category: Riess B]]
		+	[[Category: Voll MA]]

OCA at 05:18, 4 November 2020

OCA — Wed, 04 Nov 2020 05:18:37 GMT

←Older revision		Revision as of 05:18, 4 November 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7apq is ON HOLD	+	The entry 7apq is ON HOLD until Paper Publication

	Authors: Kolos, M.J., Pomplun, S., Riess, B., Purder, P., Voll, M.A., Merz, S., Bracher, A., Meyners, C., Krewald, V., Hausch, F.		Authors: Kolos, M.J., Pomplun, S., Riess, B., Purder, P., Voll, M.A., Merz, S., Bracher, A., Meyners, C., Krewald, V., Hausch, F.
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	Description: The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-(benzo[d]thiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one		Description: The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-(benzo[d]thiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Krewald, V]]
	[[Category: Voll, M.A]]		[[Category: Voll, M.A]]
		+	[[Category: Merz, S]]
		+	[[Category: Purder, P]]
	[[Category: Pomplun, S]]		[[Category: Pomplun, S]]
	[[Category: Meyners, C]]		[[Category: Meyners, C]]
		+	[[Category: Hausch, F]]
	[[Category: Kolos, M.J]]		[[Category: Kolos, M.J]]
	[[Category: Bracher, A]]		[[Category: Bracher, A]]
	[[Category: Riess, B]]		[[Category: Riess, B]]
-	[[Category: Krewald, V]]
-	[[Category: Merz, S]]
-	[[Category: Purder, P]]
-	[[Category: Hausch, F]]

OCA: Protected "7apq" [edit=sysop:move=sysop]

OCA — Wed, 28 Oct 2020 18:56:24 GMT

Protected "7apq" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:56, 28 October 2020

OCA: New page: '''Unreleased structure''' The entry 7apq is ON HOLD Authors: Kolos, M.J., Pomplun, S., Riess, B., Purder, P., Voll, M.A., Merz, S., Bracher, A., Meyners, C., Krewald, V., Hausch, F. D...

OCA — Wed, 28 Oct 2020 18:56:23 GMT

New page: '''Unreleased structure''' The entry 7apq is ON HOLD Authors: Kolos, M.J., Pomplun, S., Riess, B., Purder, P., Voll, M.A., Merz, S., Bracher, A., Meyners, C., Krewald, V., Hausch, F. D...

New page

'''Unreleased structure'''

The entry 7apq is ON HOLD

Authors: Kolos, M.J., Pomplun, S., Riess, B., Purder, P., Voll, M.A., Merz, S., Bracher, A., Meyners, C., Krewald, V., Hausch, F.

Description: The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-(benzo[d]thiazol-6-ylsulfonyl)-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one
[[Category: Unreleased Structures]]
[[Category: Voll, M.A]]
[[Category: Pomplun, S]]
[[Category: Meyners, C]]
[[Category: Kolos, M.J]]
[[Category: Bracher, A]]
[[Category: Riess, B]]
[[Category: Krewald, V]]
[[Category: Merz, S]]
[[Category: Purder, P]]
[[Category: Hausch, F]]