6qyk - Revision history

OCA at 12:11, 24 January 2024

OCA — Wed, 24 Jan 2024 12:11:12 GMT

←Older revision		Revision as of 12:11, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6qyk' size='340' side='right'caption='[[6qyk]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='6qyk' size='340' side='right'caption='[[6qyk]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qyk]] 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=6QYK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QYK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qyk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=6QYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QYK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JLB:(2~{R})-2-[6-ethyl-5-(1~{H}-indol-5-yl)thieno[2,3-d]pyrimidin-4-yl]oxypropanoic+acid'>JLB</scene>, <scene name='pdbligand=~~MAL~~:~~MALTOSE~~'>~~MAL~~</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]] 2.3Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qxj\|6qxj]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=JLB:(2~{R})-2-[6-ethyl-5-(1~{H}-indol-5-yl)thieno[2,3-d]pyrimidin-4-yl]oxypropanoic+acid'>JLB</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=6qyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qyk OCA], [https://pdbe.org/6qyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qyk RCSB], [https://www.ebi.ac.uk/pdbsum/6qyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qyk ProSAT]</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=6qyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qyk OCA], [~~http~~://pdbe.org/6qyk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qyk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qyk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qyk 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 ==
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	</div>		</div>
	<div class="pdbe-citations 6qyk" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6qyk" 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]]
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cauquil, N]]	+	[[Category: Cauquil N]]
-	[[Category: Chen, I]]	+	[[Category: Chen I]]
-	[[Category: Csekei, M]]	+	[[Category: Csekei M]]
-	[[Category: Davidson, J]]	+	[[Category: Davidson J]]
-	[[Category: Davis, B]]	+	[[Category: Davis B]]
-	[[Category: Demarles, D]]	+	[[Category: Demarles D]]
-	[[Category: Dokurno, P]]	+	[[Category: Dokurno P]]
-	[[Category: Geneste, O]]	+	[[Category: Geneste O]]
-	[[Category: Hubbard~~, R E~~]]	+	[[Category: Hubbard RE]]
-	[[Category: Kotschy, A]]	+	[[Category: Kotschy A]]
-	[[Category: LeToumelin-Braizat, G]]	+	[[Category: LeToumelin-Braizat G]]
-	[[Category: Murray, J]]	+	[[Category: Murray J]]
-	[[Category: Ondi, L]]	+	[[Category: Ondi L]]
-	[[Category: Paczal, A]]	+	[[Category: Paczal A]]
-	[[Category: Pedder, C]]	+	[[Category: Pedder C]]
-	[[Category: Perron-Sierra, F]]	+	[[Category: Perron-Sierra F]]
-	[[Category: Radics, G]]	+	[[Category: Radics G]]
-	[[Category: Robertson, A]]	+	[[Category: Robertson A]]
-	[[Category: Smith, J]]	+	[[Category: Smith J]]
-	[[Category: Surgenor~~, A E~~]]	+	[[Category: Surgenor AE]]
-	[[Category: Szabo~~, Z B~~]]	+	[[Category: Szabo ZB]]
-	[[Category: Szlavik, Z]]	+	[[Category: Szlavik Z]]
-	[[Category: Zarka, M]]	+	[[Category: Zarka M]]
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Apoptosis-inhibitor complex]]~~	+
-	~~[[Category: Mbp]]~~	+
-	~~[[Category: Mcl1]]~~	+
-	~~[[Category: Small molecule inhibitor~~]]	+

OCA at 06:48, 21 August 2019

OCA — Wed, 21 Aug 2019 06:48:28 GMT

←Older revision		Revision as of 06:48, 21 August 2019
Line 3:		Line 3:
	<StructureSection load='6qyk' size='340' side='right'caption='[[6qyk]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='6qyk' size='340' side='right'caption='[[6qyk]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qyk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QYK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qyk]] 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=6QYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QYK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JLB:(2~{R})-2-[6-ethyl-5-(1~{H}-indol-5-yl)thieno[2,3-d]pyrimidin-4-yl]oxypropanoic+acid'>JLB</scene>, <scene name='pdbligand=MAL:MALTOSE'>MAL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JLB:(2~{R})-2-[6-ethyl-5-(1~{H}-indol-5-yl)thieno[2,3-d]pyrimidin-4-yl]oxypropanoic+acid'>JLB</scene>, <scene name='pdbligand=MAL:MALTOSE'>MAL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qxj\|6qxj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qxj\|6qxj]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qyk OCA], [http://pdbe.org/6qyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qyk RCSB], [http://www.ebi.ac.uk/pdbsum/6qyk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qyk ProSAT]</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=6qyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qyk OCA], [http://pdbe.org/6qyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qyk RCSB], [http://www.ebi.ac.uk/pdbsum/6qyk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qyk ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Cauquil, N]]		[[Category: Cauquil, N]]

OCA at 06:03, 7 August 2019

OCA — Wed, 07 Aug 2019 06:03:00 GMT

←Older revision		Revision as of 06:03, 7 August 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qyk is ~~ON HOLD until Paper~~ Publication	+	==Structure of MBP-Mcl-1 in complex with compound 7a==
		+	<StructureSection load='6qyk' size='340' side='right'caption='[[6qyk]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6qyk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QYK FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JLB:(2~{R})-2-[6-ethyl-5-(1~{H}-indol-5-yl)thieno[2,3-d]pyrimidin-4-yl]oxypropanoic+acid'>JLB</scene>, <scene name='pdbligand=MAL:MALTOSE'>MAL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qxj\|6qxj]]</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=6qyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qyk OCA], [http://pdbe.org/6qyk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qyk RCSB], [http://www.ebi.ac.uk/pdbsum/6qyk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qyk ProSAT]</span></td></tr>
		+	</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), an antiapoptotic member of the Bcl-2 family of proteins, whose upregulation when observed in human cancers is associated with high tumor grade, poor survival, and resistance to chemotherapy, has emerged as an attractive target for cancer therapy. Here, we report the discovery of selective small molecule inhibitors of Mcl-1 that inhibit cellular activity. Fragment screening identified thienopyrimidine amino acids as promising but nonselective hits that were optimized using nuclear magnetic resonance and X-ray-derived structural information. The introduction of hindered rotation along a biaryl axis has conferred high selectivity to the compounds, and cellular activity was brought on scale by offsetting the negative charge of the anchoring carboxylate group. The obtained compounds described here exhibit nanomolar binding affinity and mechanism-based cellular efficacy, caspase induction, and growth inhibition. These early research efforts illustrate drug discovery optimization from thienopyrimidine hits to a lead compound, the chemical series leading to the identification of our more advanced compounds S63845 and S64315.

-	~~Authors: Dokurno, P~~., Szlavik, Z., Ondi, L., Csekei, M., Paczal, A., Szabo~~, Z.B.~~, Radics, G., Murray, J., Davidson, J., Chen, I., Davis, B., Hubbard~~, R.E.~~, Pedder, C., Surgenor, A~~.E.~~, Smith, J., Robertson, A., LeToumelin-Braizat, G., Cauquil, N., Zarka, M., Demarles, D., Perron-Sierra, F., Geneste, O., Kotschy, A.	+	Structure-Guided Discovery of a Selective Mcl-1 Inhibitor with Cellular Activity.,Szlavik Z, Ondi L, Csekei M, Paczal A, Szabo ZB, Radics G, Murray J, Davidson J, Chen I, Davis B, Hubbard RE, Pedder C, Dokurno P, Surgenor A, Smith J, Robertson A, LeToumelin-Braizat G, Cauquil N, Zarka M, Demarles D, Perron-Sierra F, Claperon A, Colland F, Geneste O, Kotschy A J Med Chem. 2019 Jul 24. doi: 10.1021/acs.jmedchem.9b00134. PMID:31339316<ref>PMID:31339316</ref>

-	~~Description: Structure~~ of ~~MBP~~-~~Mcl~~-~~1 in complex with compound 7a~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6qyk" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Cauquil, N]]
		+	[[Category: Chen, I]]
		+	[[Category: Csekei, M]]
		+	[[Category: Davidson, J]]
		+	[[Category: Davis, B]]
		+	[[Category: Demarles, D]]
		+	[[Category: Dokurno, P]]
		+	[[Category: Geneste, O]]
		+	[[Category: Hubbard, R E]]
		+	[[Category: Kotschy, A]]
		+	[[Category: LeToumelin-Braizat, G]]
		+	[[Category: Murray, J]]
		+	[[Category: Ondi, L]]
	[[Category: Paczal, A]]		[[Category: Paczal, A]]
	[[Category: Pedder, C]]		[[Category: Pedder, C]]
	[[Category: Perron-Sierra, F]]		[[Category: Perron-Sierra, F]]
-	[[Category: ~~Demarles~~, ~~D]]~~	+	[[Category: Radics, G]]
-	~~[[Category: Chen, I~~]]	+
	[[Category: Robertson, A]]		[[Category: Robertson, A]]
	[[Category: Smith, J]]		[[Category: Smith, J]]
-	[[Category: ~~Ondi~~, ~~L]]~~	+	[[Category: Surgenor, A E]]
-	~~[[Category: Davidson, J]]~~	+	[[Category: Szabo, Z B]]
-	~~[[Category: Radics, G]]~~	+
-	~~[[Category: Zarka, M]]~~	+
-	~~[[Category: Hubbard, R.~~E]]	+
-	[[Category: ~~Letoumelin-Braizat, G]]~~	+
-	~~[[Category: Davis~~, B]]	+
	[[Category: Szlavik, Z]]		[[Category: Szlavik, Z]]
-	[[Category: ~~Surgenor~~, ~~A.E~~]]	+	[[Category: Zarka, M]]
-	[[Category: ~~Murray, J~~]]	+	[[Category: Apoptosis]]
-	[[Category: ~~Dokurno, P~~]]	+	[[Category: Apoptosis-inhibitor complex]]
-	[[Category: ~~Kotschy, A~~]]	+	[[Category: Mbp]]
-	[[Category: ~~Cauquil, N~~]]	+	[[Category: Mcl1]]
-	[[Category: ~~Geneste, O]]~~	+	[[Category: Small molecule inhibitor]]
-	~~[[Category: Csekei, M]]~~	+
-	~~[[Category: Szabo, Z.B~~]]	+

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

OCA — Wed, 20 Mar 2019 06:09:05 GMT

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

←Older revision

Revision as of 06:09, 20 March 2019

OCA: New page: '''Unreleased structure''' The entry 6qyk is ON HOLD until Paper Publication Authors: Dokurno, P., Szlavik, Z., Ondi, L., Csekei, M., Paczal, A., Szabo, Z.B., Radics, G., Murray, J., Da...

OCA — Wed, 20 Mar 2019 06:09:04 GMT

New page: '''Unreleased structure''' The entry 6qyk is ON HOLD until Paper Publication Authors: Dokurno, P., Szlavik, Z., Ondi, L., Csekei, M., Paczal, A., Szabo, Z.B., Radics, G., Murray, J., Da...

New page

'''Unreleased structure'''

The entry 6qyk is ON HOLD until Paper Publication

Authors: Dokurno, P., Szlavik, Z., Ondi, L., Csekei, M., Paczal, A., Szabo, Z.B., Radics, G., Murray, J., Davidson, J., Chen, I., Davis, B., Hubbard, R.E., Pedder, C., Surgenor, A.E., Smith, J., Robertson, A., LeToumelin-Braizat, G., Cauquil, N., Zarka, M., Demarles, D., Perron-Sierra, F., Geneste, O., Kotschy, A.

Description: Structure of MBP-Mcl-1 in complex with compound 7a
[[Category: Unreleased Structures]]
[[Category: Paczal, A]]
[[Category: Pedder, C]]
[[Category: Perron-Sierra, F]]
[[Category: Demarles, D]]
[[Category: Chen, I]]
[[Category: Robertson, A]]
[[Category: Smith, J]]
[[Category: Ondi, L]]
[[Category: Davidson, J]]
[[Category: Radics, G]]
[[Category: Zarka, M]]
[[Category: Hubbard, R.E]]
[[Category: Letoumelin-Braizat, G]]
[[Category: Davis, B]]
[[Category: Szlavik, Z]]
[[Category: Surgenor, A.E]]
[[Category: Murray, J]]
[[Category: Dokurno, P]]
[[Category: Kotschy, A]]
[[Category: Cauquil, N]]
[[Category: Geneste, O]]
[[Category: Csekei, M]]
[[Category: Szabo, Z.B]]