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4oq5
From Proteopedia
(Difference between revisions)
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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== | |
| - | + | <StructureSection load='4oq5' size='340' side='right' caption='[[4oq5]], [[Resolution|resolution]] 2.86Å' scene=''> | |
| - | { | + | == Structural highlights == |
| - | + | <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> | |
| - | ==Function== | + | </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> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oq6|4oq6]]</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=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> | ||
| + | </table> | ||
| + | == Function == | ||
[[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> | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| + | |||
| + | 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> | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | + | *[[Bcl-2|Bcl-2]] | |
| - | [[Category: Kunzer, A R | + | == References == |
| - | [[Category: Park, C | + | <references/> |
| - | [[Category: Petros, A M | + | __TOC__ |
| - | [[Category: Song, D | + | </StructureSection> |
| - | [[Category: Souers, A J | + | [[Category: Human]] |
| - | [[Category: Sun, C | + | [[Category: Kunzer, A R]] |
| - | [[Category: Swann, S L | + | [[Category: Park, C]] |
| - | [[Category: Swinger, K | + | [[Category: Petros, A M]] |
| - | [[Category: Wendt, M D | + | [[Category: Song, D]] |
| - | [[Category: Zhang, H | + | [[Category: Souers, A J]] |
| + | [[Category: Sun, C]] | ||
| + | [[Category: Swann, S L]] | ||
| + | [[Category: Swinger, K]] | ||
| + | [[Category: Wendt, M D]] | ||
| + | [[Category: Zhang, H]] | ||
[[Category: Apoptosis-inhibitor complex]] | [[Category: Apoptosis-inhibitor complex]] | ||
Revision as of 21:49, 25 December 2014
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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Categories: Human | Kunzer, A R | Park, C | Petros, A M | Song, D | Souers, A J | Sun, C | Swann, S L | Swinger, K | Wendt, M D | Zhang, H | Apoptosis-inhibitor complex
