7okd - Revision history

OCA at 12:51, 1 February 2024

2024-02-01T12:51:39Z

←Older revision		Revision as of 12:51, 1 February 2024
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	<StructureSection load='7okd' size='340' side='right'caption='[[7okd]], [[Resolution\|resolution]] 1.94Å' scene=''>		<StructureSection load='7okd' size='340' side='right'caption='[[7okd]], [[Resolution\|resolution]] 1.94Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7okd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7okd]] 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=7OKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VGW:2-chloranyl-4-[[4-[2-(5-cyclopropylpyrimidin-2-yl)propan-2-ylamino]-1-methyl-2-oxidanylidene-quinolin-6-yl]amino]pyridine-3-carbonitrile'>VGW</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]] 1.94Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VGW:2-chloranyl-4-[[4-[2-(5-cyclopropylpyrimidin-2-yl)propan-2-ylamino]-1-methyl-2-oxidanylidene-quinolin-6-yl]amino]pyridine-3-carbonitrile'>VGW</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=7okd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okd OCA], [https://pdbe.org/7okd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okd RCSB], [https://www.ebi.ac.uk/pdbsum/7okd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okd 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=7okd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okd OCA], [https://pdbe.org/7okd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okd RCSB], [https://www.ebi.ac.uk/pdbsum/7okd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN]] Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.	+	[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN] Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN]] Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.<ref>PMID:9649500</ref> <ref>PMID:18280243</ref>	+	[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN] Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.<ref>PMID:9649500</ref> <ref>PMID:18280243</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Bihan, Y V.Le~~]]	+	[[Category: Gunnell EA]]
-	[[Category: ~~Gunnell, E A~~]]	+	[[Category: Le Bihan Y-V]]
-	[[Category: Montfort~~, R L.M van]]~~	+	[[Category: Van Montfort RLM]]
-	~~[[Category: Cancer]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Lymphoma]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 15:38, 22 December 2021

2021-12-22T15:38:18Z

←Older revision		Revision as of 15:38, 22 December 2021
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	==Crystal structure of human BCL6 BTB domain in complex with compound 25==		==Crystal structure of human BCL6 BTB domain in complex with compound 25==
-	<StructureSection load='7okd' size='340' side='right'caption='[[7okd]]' scene=''>	+	<StructureSection load='7okd' size='340' side='right'caption='[[7okd]], [[Resolution\|resolution]] 1.94Å' 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=7OKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7okd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKD 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=7okd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okd OCA], [https://pdbe.org/7okd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okd RCSB], [https://www.ebi.ac.uk/pdbsum/7okd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okd 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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VGW:2-chloranyl-4-[[4-[2-(5-cyclopropylpyrimidin-2-yl)propan-2-ylamino]-1-methyl-2-oxidanylidene-quinolin-6-yl]amino]pyridine-3-carbonitrile'>VGW</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=7okd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okd OCA], [https://pdbe.org/7okd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okd RCSB], [https://www.ebi.ac.uk/pdbsum/7okd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okd ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN]] Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN]] Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.<ref>PMID:9649500</ref> <ref>PMID:18280243</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We describe the optimization of modestly active starting points to potent inhibitors of BCL6 by growing into a subpocket, which was occupied by a network of five stably bound water molecules. Identifying potent inhibitors required not only forming new interactions in the subpocket but also perturbing the water network in a productive, potency-increasing fashion while controlling the physicochemical properties. We achieved this goal in a sequential manner by systematically probing the pocket and the water network, ultimately achieving a 100-fold improvement of activity. The most potent compounds displaced three of the five initial water molecules and formed hydrogen bonds with the remaining two. Compound 25 showed a promising profile for a lead compound with submicromolar inhibition of BCL6 in cells and satisfactory pharmacokinetic (PK) properties. Our work highlights the importance of finding productive ways to perturb existing water networks when growing into solvent-filled protein pockets.
		+
		+	Into Deep Water: Optimizing BCL6 Inhibitors by Growing into a Solvated Pocket.,Lloyd MG, Huckvale R, Cheung KJ, Rodrigues MJ, Collie GW, Pierrat OA, Gatti Iou M, Carter M, Davis OA, McAndrew PC, Gunnell E, Le Bihan YV, Talbot R, Henley AT, Johnson LD, Hayes A, Bright MD, Raynaud FI, Meniconi M, Burke R, van Montfort RLM, Rossanese OW, Bellenie BR, Hoelder S J Med Chem. 2021 Nov 30. doi: 10.1021/acs.jmedchem.1c00946. PMID:34846884<ref>PMID:34846884</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7okd" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Gunnell EA~~]]	+	[[Category: Bihan, Y V.Le]]
-	[[Category: ~~Le Bihan Y-V~~]]	+	[[Category: Gunnell, E A]]
-	[[Category: ~~Van~~ Montfort ~~RLM~~]]	+	[[Category: Montfort, R L.M van]]
		+	[[Category: Cancer]]
		+	[[Category: Inhibitor]]
		+	[[Category: Lymphoma]]
		+	[[Category: Transcription]]

OCA at 09:56, 8 December 2021

2021-12-08T09:56:17Z

←Older revision		Revision as of 09:56, 8 December 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7okd ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of human BCL6 BTB domain in complex with compound 25==
-		+	<StructureSection load='7okd' size='340' side='right'caption='[[7okd]]' scene=''>
-	~~Authors~~: ~~Gunnell~~, E.A., ~~Le Bihan~~, Y.-V., ~~van Montfort, R~~.L.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKD FirstGlance]. <br>
-	~~Description: Crystal structure of human BCL6 BTB domain in complex with compound 25~~	+	</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=7okd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okd OCA], [https://pdbe.org/7okd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okd RCSB], [https://www.ebi.ac.uk/pdbsum/7okd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okd ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Van Montfort, R.L.M~~]]	+	__TOC__
-	[[Category: Le Bihan, Y.-V]]	+	</StructureSection>
-	[[Category: ~~Gunnell, E.A~~]]	+	[[Category: Large Structures]]
		+	[[Category: Gunnell EA]]
		+	[[Category: Le Bihan Y-V]]
		+	[[Category: Van Montfort RLM]]

OCA at 13:47, 17 June 2021

2021-06-17T13:47:52Z

←Older revision		Revision as of 13:47, 17 June 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Gunnell, E.A., Le Bihan, Y.-V., van Montfort, R.L.M.		Authors: Gunnell, E.A., Le Bihan, Y.-V., van Montfort, R.L.M.

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

2021-05-26T08:09:30Z

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

←Older revision

Revision as of 08:09, 26 May 2021

OCA: New page: '''Unreleased structure''' The entry 7okd is ON HOLD Authors: Gunnell, E.A., Le Bihan, Y.-V., van Montfort, R.L.M. Description: Crystal structure of human BCL6 BTB domain in complex wi...

2021-05-26T08:09:28Z

New page: '''Unreleased structure''' The entry 7okd is ON HOLD Authors: Gunnell, E.A., Le Bihan, Y.-V., van Montfort, R.L.M. Description: Crystal structure of human BCL6 BTB domain in complex wi...

New page

'''Unreleased structure'''

The entry 7okd is ON HOLD

Authors: Gunnell, E.A., Le Bihan, Y.-V., van Montfort, R.L.M.

Description: Crystal structure of human BCL6 BTB domain in complex with compound 25
[[Category: Unreleased Structures]]
[[Category: Van Montfort, R.L.M]]
[[Category: Le Bihan, Y.-V]]
[[Category: Gunnell, E.A]]