4oq5

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==Crystal Structure of Human MCL-1 Bound to Inhibitor 4-(4-methylnaphthalen-1-yl)-2-{[(4-phenoxyphenyl)sulfonyl]amino}benzoic acid==
==Crystal Structure of Human MCL-1 Bound to Inhibitor 4-(4-methylnaphthalen-1-yl)-2-{[(4-phenoxyphenyl)sulfonyl]amino}benzoic acid==
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<StructureSection load='4oq5' size='340' side='right' caption='[[4oq5]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
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<StructureSection load='4oq5' size='340' side='right'caption='[[4oq5]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4oq5]] is a 6 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=4OQ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OQ5 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4oq5]] is a 6 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=4OQ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OQ5 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2UU:4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL)SULFONYL]AMINO}BENZOIC+ACID'>2UU</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.86&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oq6|4oq6]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2UU:4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL)SULFONYL]AMINO}BENZOIC+ACID'>2UU</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4oq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq5 OCA], [https://pdbe.org/4oq5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oq5 RCSB], [https://www.ebi.ac.uk/pdbsum/4oq5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oq5 ProSAT]</span></td></tr>
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<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=4oq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oq5 RCSB], [http://www.ebi.ac.uk/pdbsum/4oq5 PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of malignant cells. One way in which cancer cells achieve this evasion is thru overexpression of the pro-survival members of the BCL-2 family. Overexpression of MCL-1, a pro-survival protein, has been shown to be a resistance factor for Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of fragment screening methods and structural biology to drive the discovery of novel MCL-1 inhibitors from two distinct structural classes. Specifically, cores derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR-based fragment screen and elaborated using high throughput analog synthesis. This culminated in the discovery of selective and potent inhibitors of MCL-1 that may serve as promising leads for medicinal chemistry optimization efforts.
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Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein.,Petros AM, Swann SL, Song D, Swinger K, Park C, Zhang H, Wendt MD, Kunzer AR, Souers AJ, Sun C Bioorg Med Chem Lett. 2014 Mar 15;24(6):1484-8. doi: 10.1016/j.bmcl.2014.02.010. , Epub 2014 Feb 14. PMID:24582986<ref>PMID:24582986</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Bcl-2|Bcl-2]]
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*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Kunzer, A R]]
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[[Category: Large Structures]]
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[[Category: Park, C]]
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[[Category: Kunzer AR]]
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[[Category: Petros, A M]]
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[[Category: Park C]]
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[[Category: Song, D]]
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[[Category: Petros AM]]
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[[Category: Souers, A J]]
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[[Category: Song D]]
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[[Category: Sun, C]]
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[[Category: Souers AJ]]
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[[Category: Swann, S L]]
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[[Category: Sun C]]
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[[Category: Swinger, K]]
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[[Category: Swann SL]]
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[[Category: Wendt, M D]]
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[[Category: Swinger K]]
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[[Category: Zhang, H]]
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[[Category: Wendt MD]]
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[[Category: Apoptosis-inhibitor complex]]
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[[Category: Zhang H]]

Current revision

Crystal Structure of Human MCL-1 Bound to Inhibitor 4-(4-methylnaphthalen-1-yl)-2-{[(4-phenoxyphenyl)sulfonyl]amino}benzoic acid

PDB ID 4oq5

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