6ybj - Revision history

OCA at 13:23, 24 January 2024

OCA — Wed, 24 Jan 2024 13:23:28 GMT

←Older revision		Revision as of 13:23, 24 January 2024
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	<StructureSection load='6ybj' size='340' side='right'caption='[[6ybj]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6ybj' size='340' side='right'caption='[[6ybj]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ybj]] 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=6YBJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6YBJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ybj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YBJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=OJW:(2~{R})-2-[5-[3-chloranyl-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-6-(5-fluoranylfuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy-3-[2-[(2-methylpyrazol-3-yl)methoxy]phenyl]propanoic+acid'>OJW</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]] 2.5Å</td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat"><div style='overflow: auto; max~~-~~height: 3em;~~'>~~[[6ybg\|6ybg]], [[6ybk\|6ybk]], [[6ybl\|6ybl]]~~</~~div~~>~~</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=OJW:(2~{R})-2-[5-[3-chloranyl-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-6-(5-fluoranylfuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy-3-[2-[(2-methylpyrazol-3-yl)methoxy]phenyl]propanoic+acid'>OJW</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MCL1, BCL2L3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=6ybj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ybj OCA], [https://pdbe.org/6ybj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ybj RCSB], [https://www.ebi.ac.uk/pdbsum/6ybj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ybj ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6ybj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ybj OCA], [~~http~~://pdbe.org/6ybj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ybj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ybj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ybj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~MALE_ECO57 MALE_ECO57]~~] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides ~~(By similarity)~~.	+	[https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[https://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6ybj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ybj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[B-cell lymphoma proteins 3D structures\|B-cell lymphoma proteins 3D structures]]
		+	*[[Maltose-binding protein 3D structures\|Maltose-binding protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Escherichia coli O157:H7]]
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dokurno, P]]	+	[[Category: Dokurno P]]
-	[[Category: Murray~~, J B~~]]	+	[[Category: Murray JB]]
-	[[Category: Surgenor~~, A E]]~~	+	[[Category: Surgenor AE]]
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Apoptosis-inhibitor complex]]~~	+
-	~~[[Category: Mbp]]~~	+
-	~~[[Category: Mcl-1]]~~	+
-	~~[[Category: S64315]]~~	+
-	~~[[Category: Small molecule inhibitor~~]]	+

OCA at 08:14, 2 December 2020

OCA — Wed, 02 Dec 2020 08:14:26 GMT

←Older revision		Revision as of 08:14, 2 December 2020
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	==Structure of MBP-Mcl-1 in complex with compound 3e==		==Structure of MBP-Mcl-1 in complex with compound 3e==
-	<StructureSection load='6ybj' size='340' side='right'caption='[[6ybj]]' scene=''>	+	<StructureSection load='6ybj' size='340' side='right'caption='[[6ybj]], [[Resolution\|resolution]] 2.50Å' 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=6YBJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YBJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ybj]] 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=6YBJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YBJ FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ybj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ybj OCA], [http://pdbe.org/6ybj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ybj RCSB], [http://www.ebi.ac.uk/pdbsum/6ybj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ybj 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=OJW:(2~{R})-2-[5-[3-chloranyl-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-6-(5-fluoranylfuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy-3-[2-[(2-methylpyrazol-3-yl)methoxy]phenyl]propanoic+acid'>OJW</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6ybg\|6ybg]], [[6ybk\|6ybk]], [[6ybl\|6ybl]]</div></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MCL1, BCL2L3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ybj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ybj OCA], [http://pdbe.org/6ybj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ybj RCSB], [http://www.ebi.ac.uk/pdbsum/6ybj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ybj ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MALE_ECO57 MALE_ECO57]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Myeloid cell leukemia 1 (Mcl-1) has emerged as an attractive target for cancer therapy. It is an antiapoptotic member of the Bcl-2 family of proteins, whose upregulation in human cancers is associated with high tumor grade, poor survival, and resistance to chemotherapy. Here we report the discovery of our clinical candidate S64315, a selective small molecule inhibitor of Mcl-1. Starting from a fragment derived lead compound, we have conducted structure guided optimization that has led to a significant (3 log) improvement of target affinity as well as cellular potency. The presence of hindered rotation along a biaryl axis has conferred high selectivity to the compounds against other members of the Bcl-2 family. During optimization, we have also established predictive PD markers of Mcl-1 inhibition and achieved both efficient in vitro cell killing and tumor regression in Mcl-1 dependent cancer models. The preclinical candidate has drug-like properties that have enabled its development and entry into clinical trials.
		+
		+	Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor.,Szlavik Z, Csekei M, Paczal A, Szabo ZB, Sipos S, Radics G, Proszenyak A, Balint B, Murray J, Davidson J, Chen I, Dokurno P, Surgenor AE, Daniels ZM, Hubbard RE, Le Toumelin-Braizat G, Claperon A, Lysiak-Auvity G, Girard AM, Bruno A, Chanrion M, Colland F, Maragno AL, Demarles D, Geneste O, Kotschy A J Med Chem. 2020 Nov 4. doi: 10.1021/acs.jmedchem.0c01234. PMID:33146521<ref>PMID:33146521</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6ybj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dokurno P]]	+	[[Category: Dokurno, P]]
-	[[Category: Murray JB]]	+	[[Category: Murray, J B]]
-	[[Category: Surgenor AE]]	+	[[Category: Surgenor, A E]]
		+	[[Category: Apoptosis]]
		+	[[Category: Apoptosis-inhibitor complex]]
		+	[[Category: Mbp]]
		+	[[Category: Mcl-1]]
		+	[[Category: S64315]]
		+	[[Category: Small molecule inhibitor]]

OCA at 09:38, 18 November 2020

OCA — Wed, 18 Nov 2020 09:38:22 GMT

←Older revision		Revision as of 09:38, 18 November 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ybj ~~is ON HOLD until Paper Publication~~	+	==Structure of MBP-Mcl-1 in complex with compound 3e==
-		+	<StructureSection load='6ybj' size='340' side='right'caption='[[6ybj]]' scene=''>
-	~~Authors~~: ~~Dokurno~~, P., ~~Surgenor~~, A.E., ~~Murray~~, J.B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YBJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YBJ FirstGlance]. <br>
-	~~Description: Structure of MBP-Mcl-1 in complex with compound 3e~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ybj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ybj OCA], [http://pdbe.org/6ybj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ybj RCSB], [http://www.ebi.ac.uk/pdbsum/6ybj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ybj ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Murray, J.B~~]]	+	__TOC__
-	[[Category: ~~Surgenor, A.E~~]]	+	</StructureSection>
-	[[Category: ~~Dokurno, P~~]]	+	[[Category: Large Structures]]
		+	[[Category: Dokurno P]]
		+	[[Category: Murray JB]]
		+	[[Category: Surgenor AE]]

OCA at 07:39, 1 April 2020

OCA — Wed, 01 Apr 2020 07:39:41 GMT

←Older revision		Revision as of 07:39, 1 April 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ybj is ON HOLD	+	The entry 6ybj is ON HOLD until Paper Publication

	Authors: Dokurno, P., Surgenor, A.E., Murray, J.B.		Authors: Dokurno, P., Surgenor, A.E., Murray, J.B.

OCA: Protected "6ybj" [edit=sysop:move=sysop]

OCA — Fri, 27 Mar 2020 08:35:49 GMT

Protected "6ybj" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:35, 27 March 2020

OCA: New page: '''Unreleased structure''' The entry 6ybj is ON HOLD Authors: Dokurno, P., Surgenor, A.E., Murray, J.B. Description: Structure of MBP-Mcl-1 in complex with compound 3e [[Category: Unre...

OCA — Fri, 27 Mar 2020 08:35:48 GMT

New page: '''Unreleased structure''' The entry 6ybj is ON HOLD Authors: Dokurno, P., Surgenor, A.E., Murray, J.B. Description: Structure of MBP-Mcl-1 in complex with compound 3e [[Category: Unre...

New page

'''Unreleased structure'''

The entry 6ybj is ON HOLD

Authors: Dokurno, P., Surgenor, A.E., Murray, J.B.

Description: Structure of MBP-Mcl-1 in complex with compound 3e
[[Category: Unreleased Structures]]
[[Category: Murray, J.B]]
[[Category: Surgenor, A.E]]
[[Category: Dokurno, P]]