4dro - Revision history

OCA at 14:43, 14 March 2024

OCA — Thu, 14 Mar 2024 14:43:05 GMT

←Older revision		Revision as of 14:43, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dro]] 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=4DRO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DRO FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dro]] 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=4DRO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DRO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MD:{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC+ACID'>0MD</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]] 1.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MD:{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC+ACID'>0MD</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=4dro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dro OCA], [https://pdbe.org/4dro PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dro RCSB], [https://www.ebi.ac.uk/pdbsum/4dro PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dro 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=4dro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dro OCA], [https://pdbe.org/4dro PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dro RCSB], [https://www.ebi.ac.uk/pdbsum/4dro PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dro 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.	+
-		+
-	Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52.,Gopalakrishnan R, Kozany C, Gaali S, Kress C, Hoogeland B, Bracher A, Hausch F J Med Chem. 2012 May 10;55(9):4114-22. Epub 2012 Apr 19. PMID:22455444<ref>PMID:22455444</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4dro" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[FKBP 3D structures\|FKBP 3D structures]]		*[[FKBP 3D structures\|FKBP 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:35, 21 September 2022

OCA — Wed, 21 Sep 2022 08:35:34 GMT

←Older revision		Revision as of 08:35, 21 September 2022
Line 1:		Line 1:

	==EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)-3-(3,4-dimethoxyphenyl)-1-phenylpropyl (2S)-1-{[(1R,2S)-2-ethyl-1-hydroxycyclohexyl](oxo)acetyl}piperidine-2-carboxylate==		==EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)-3-(3,4-dimethoxyphenyl)-1-phenylpropyl (2S)-1-{[(1R,2S)-2-ethyl-1-hydroxycyclohexyl](oxo)acetyl}piperidine-2-carboxylate==
-	<StructureSection load='4dro' size='340' side='right' caption='[[4dro]], [[Resolution\|resolution]] 1.10Å' scene=''>	+	<StructureSection load='4dro' size='340' side='right'caption='[[4dro]], [[Resolution\|resolution]] 1.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4dro]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DRO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4DRO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4dro]] 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=4DRO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DRO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MD:{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC+ACID'>0MD</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MD:{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC+ACID'>0MD</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4drk\|4drk]], [[4drm\|4drm]], [[4drn\|4drn]], [[4drp\|4drp]], [[4drq\|4drq]]</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=4dro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dro OCA], [https://pdbe.org/4dro PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dro RCSB], [https://www.ebi.ac.uk/pdbsum/4dro PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dro ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AIG6, FKBP5, FKBP51 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4dro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dro OCA], [~~http~~://pdbe.org/4dro PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4dro RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4dro PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4dro ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://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 23:		Line 20:

	==See Also==		==See Also==
-	*[[~~FK506 binding protein~~\|~~FK506 binding protein~~]]	+	*[[FKBP 3D structures\|FKBP 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Peptidylprolyl isomerase~~]]	+	[[Category: Large Structures]]
-	[[Category: Bracher, A]]	+	[[Category: Bracher A]]
-	[[Category: Gaali, S]]	+	[[Category: Gaali S]]
-	[[Category: Gopalakrishnan, R]]	+	[[Category: Gopalakrishnan R]]
-	[[Category: Hausch, F]]	+	[[Category: Hausch F]]
-	[[Category: Hoogeland, B]]	+	[[Category: Hoogeland B]]
-	[[Category: Kozany, C]]	+	[[Category: Kozany C]]
-	[[Category: Kress, C]]	+	[[Category: Kress C]]
-	~~[[Category: Fk-506 binding domain]]~~	+
-	~~[[Category: Hsp90 cochaperone]]~~	+
-	~~[[Category: Immunophilin]]~~	+
-	~~[[Category: Isomerase]]~~	+
-	~~[[Category: Peptidyl-prolyl isomerase~~]]	+

OCA at 14:14, 4 August 2016

OCA — Thu, 04 Aug 2016 14:14:07 GMT

←Older revision		Revision as of 14:14, 4 August 2016
Line 1:		Line 1:
		+
	==EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)-3-(3,4-dimethoxyphenyl)-1-phenylpropyl (2S)-1-{[(1R,2S)-2-ethyl-1-hydroxycyclohexyl](oxo)acetyl}piperidine-2-carboxylate==		==EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)-3-(3,4-dimethoxyphenyl)-1-phenylpropyl (2S)-1-{[(1R,2S)-2-ethyl-1-hydroxycyclohexyl](oxo)acetyl}piperidine-2-carboxylate==
	<StructureSection load='4dro' size='340' side='right' caption='[[4dro]], [[Resolution\|resolution]] 1.10Å' scene=''>		<StructureSection load='4dro' size='340' side='right' caption='[[4dro]], [[Resolution\|resolution]] 1.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4dro]] is a 1 chain structure with 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=4DRO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DRO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4dro]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DRO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DRO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MD:{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC+ACID'>0MD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MD:{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC+ACID'>0MD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4drk\|4drk]], [[4drm\|4drm]], [[4drn\|4drn]], [[4drp\|4drp]], [[4drq\|4drq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4drk\|4drk]], [[4drm\|4drm]], [[4drn\|4drn]], [[4drp\|4drp]], [[4drq\|4drq]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AIG6, FKBP5, FKBP51 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AIG6, FKBP5, FKBP51 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dro OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dro RCSB], [http://www.ebi.ac.uk/pdbsum/4dro 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=4dro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dro OCA], [http://pdbe.org/4dro PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dro RCSB], [http://www.ebi.ac.uk/pdbsum/4dro PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dro ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 4dro" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Peptidylprolyl isomerase]]		[[Category: Peptidylprolyl isomerase]]
	[[Category: Bracher, A]]		[[Category: Bracher, A]]

OCA at 15:30, 24 December 2014

OCA — Wed, 24 Dec 2014 15:30:40 GMT

←Older revision		Revision as of 15:30, 24 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4dro.~~png~~\|~~left~~\|~~200px~~]]	+	==EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)-3-(3,4-dimethoxyphenyl)-1-phenylpropyl (2S)-1-{[(1R,2S)-2-ethyl-1-hydroxycyclohexyl](oxo)acetyl}piperidine-2-carboxylate==
		+	<StructureSection load='4dro' size='340' side='right' caption='[[4dro]], [[Resolution\|resolution]] 1.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4dro]] is a 1 chain structure with 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=4DRO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DRO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MD:{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC+ACID'>0MD</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4drk\|4drk]], [[4drm\|4drm]], [[4drn\|4drn]], [[4drp\|4drp]], [[4drq\|4drq]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AIG6, FKBP5, FKBP51 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dro OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dro RCSB], [http://www.ebi.ac.uk/pdbsum/4dro PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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 ==
		+	The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.

-	<!--	+	Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52.,Gopalakrishnan R, Kozany C, Gaali S, Kress C, Hoogeland B, Bracher A, Hausch F J Med Chem. 2012 May 10;55(9):4114-22. Epub 2012 Apr 19. PMID:22455444<ref>PMID:22455444</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_4dro"~~, ~~creates the "Structure Box" on the page~~.	+
-	~~You may change the PDB parameter~~ (~~which sets the PDB file loaded into the applet~~)	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~	+
-	~~or leave the SCENE parameter empty for the default display~~.	+
-	-->	+
-	~~{{STRUCTURE_4dro\| PDB=4dro \| SCENE= }}~~	+

-	~~===EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)-3-(3~~,~~4-dimethoxyphenyl)-1-phenylpropyl (2S)-1-{[(1R,2S)-2-ethyl-1-hydroxycyclohexyl](oxo)acetyl}piperidine-2-carboxylate===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	~~<!--~~	+	*[[FK506 binding protein\|FK506 binding protein]]
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22455444}}, adds the Publication Abstract to the page~~	+	== References ==
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 22455444 is the PubMed ID number.~~	+	<references/>
-	~~-->~~	+	__TOC__
-	~~{{ABSTRACT_PUBMED_22455444}}~~	+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[~~4dro~~]] is a 1 chain structure with 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=4DRO OCA].	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022455444<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Peptidylprolyl isomerase]]		[[Category: Peptidylprolyl isomerase]]
-	[[Category: Bracher, A.]]	+	[[Category: Bracher, A]]
-	[[Category: Gaali, S.]]	+	[[Category: Gaali, S]]
-	[[Category: Gopalakrishnan, R.]]	+	[[Category: Gopalakrishnan, R]]
-	[[Category: Hausch, F.]]	+	[[Category: Hausch, F]]
-	[[Category: Hoogeland, B.]]	+	[[Category: Hoogeland, B]]
-	[[Category: Kozany, C.]]	+	[[Category: Kozany, C]]
-	[[Category: Kress, C.]]	+	[[Category: Kress, C]]
	[[Category: Fk-506 binding domain]]		[[Category: Fk-506 binding domain]]
	[[Category: Hsp90 cochaperone]]		[[Category: Hsp90 cochaperone]]

OCA at 04:56, 23 May 2012

OCA — Wed, 23 May 2012 04:56:38 GMT

←Older revision		Revision as of 04:56, 23 May 2012
Line 1:		Line 1:
-	[[Image:4dro.~~jpg~~\|left\|200px]]	+	[[Image:4dro.png\|left\|200px]]

	<!--		<!--

OCA at 09:09, 16 May 2012

OCA — Wed, 16 May 2012 09:09:18 GMT

←Older revision		Revision as of 09:09, 16 May 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4dro.jpg\|left\|200px]]

-	The ~~entry 4dro~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_4dro", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_4dro\| PDB=4dro \| SCENE= }}

-	~~Authors~~: ~~Gopalakrishnan~~, R., ~~Kozany, C., Gaali, S., Kress, C., Hoogeland, B., Bracher, A., Hausch, F.~~	+	===EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)-3-(3,4-dimethoxyphenyl)-1-phenylpropyl (2S)-1-{[(1R,2S)-2-ethyl-1-hydroxycyclohexyl](oxo)acetyl}piperidine-2-carboxylate===

-	~~Description: EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)~~-3-(3,~~4-dimethoxyphenyl)-1-phenylpropyl~~ (2S)-1-{[~~(1R,2S)-2-ethyl-~~1-~~hydroxycyclohexyl~~]~~(oxo)acetyl}piperidine~~-2-~~carboxylate~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22455444}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22455444 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22455444}}
		+
		+	==About this Structure==
		+	[[4dro]] is a 1 chain structure with 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=4DRO OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022455444</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Peptidylprolyl isomerase]]
		+	[[Category: Bracher, A.]]
		+	[[Category: Gaali, S.]]
		+	[[Category: Gopalakrishnan, R.]]
		+	[[Category: Hausch, F.]]
		+	[[Category: Hoogeland, B.]]
		+	[[Category: Kozany, C.]]
		+	[[Category: Kress, C.]]
		+	[[Category: Fk-506 binding domain]]
		+	[[Category: Hsp90 cochaperone]]
		+	[[Category: Immunophilin]]
		+	[[Category: Isomerase]]
		+	[[Category: Peptidyl-prolyl isomerase]]

OCA at 06:11, 14 March 2012

OCA — Wed, 14 Mar 2012 06:11:57 GMT

←Older revision		Revision as of 06:11, 14 March 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4dro is ON HOLD	+	The entry 4dro is ON HOLD until Paper Publication

	Authors: Gopalakrishnan, R., Kozany, C., Gaali, S., Kress, C., Hoogeland, B., Bracher, A., Hausch, F.		Authors: Gopalakrishnan, R., Kozany, C., Gaali, S., Kress, C., Hoogeland, B., Bracher, A., Hausch, F.

-	Description: ~~Evaluation of Synthetic~~ FK506 ~~Analogs as Ligands for~~ FKBP51 ~~and~~ FKBP52: ~~Complex of~~ FKBP51 ~~with 2-(3-(~~(R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(~~2-((1S~~,2R)-2-ethyl-1-~~hydroxy-cyclohexyl)-2-oxoacetyl~~)piperidine-2-~~carbonyloxy)propyl)phenoxy)acetic acid isomer b soak~~	+	Description: EVALUATION OF SYNTHETIC FK506 ANALOGS AS LIGANDS FOR FKBP51 AND FKBP52: COMPLEX OF FKBP51 WITH (1R)-3-(3,4-dimethoxyphenyl)-1-phenylpropyl (2S)-1-{[(1R,2S)-2-ethyl-1-hydroxycyclohexyl](oxo)acetyl}piperidine-2-carboxylate

OCA: Protected "4dro" [edit=sysop:move=sysop]

OCA — Wed, 29 Feb 2012 08:25:20 GMT

Protected "4dro" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:25, 29 February 2012

OCA: New page: '''Unreleased structure''' The entry 4dro is ON HOLD Authors: Gopalakrishnan, R., Kozany, C., Gaali, S., Kress, C., Hoogeland, B., Bracher, A., Hausch, F. Description: Evaluation of Sy...

OCA — Wed, 29 Feb 2012 08:25:19 GMT

New page: '''Unreleased structure''' The entry 4dro is ON HOLD Authors: Gopalakrishnan, R., Kozany, C., Gaali, S., Kress, C., Hoogeland, B., Bracher, A., Hausch, F. Description: Evaluation of Sy...

New page

'''Unreleased structure'''

The entry 4dro is ON HOLD

Authors: Gopalakrishnan, R., Kozany, C., Gaali, S., Kress, C., Hoogeland, B., Bracher, A., Hausch, F.

Description: Evaluation of Synthetic FK506 Analogs as Ligands for FKBP51 and FKBP52: Complex of FKBP51 with 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2R)-2-ethyl-1-hydroxy-cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid isomer b soak