5if4

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==Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) inhibitors using Structure-Based Design==
==Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) inhibitors using Structure-Based Design==
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<StructureSection load='5if4' size='340' side='right' caption='[[5if4]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
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<StructureSection load='5if4' size='340' side='right'caption='[[5if4]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5if4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IF4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IF4 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5if4]] is a 2 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=5IF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IF4 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=6AK:4-{8-CHLORO-11-[3-(4-CHLORO-3,5-DIMETHYLPHENOXY)PROPYL]-1-OXO-7-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)-4,5-DIHYDRO-1H-[1,4]DIAZEPINO[1,2-A]INDOL-2(3H)-YL}-1-METHYL-1H-INDOLE-6-CARBOXYLIC+ACID'>6AK</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]] 2.392&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5iez|5iez]]</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=6AK:4-{8-CHLORO-11-[3-(4-CHLORO-3,5-DIMETHYLPHENOXY)PROPYL]-1-OXO-7-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)-4,5-DIHYDRO-1H-[1,4]DIAZEPINO[1,2-A]INDOL-2(3H)-YL}-1-METHYL-1H-INDOLE-6-CARBOXYLIC+ACID'>6AK</scene></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=5if4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5if4 OCA], [http://pdbe.org/5if4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5if4 RCSB], [http://www.ebi.ac.uk/pdbsum/5if4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5if4 ProSAT]</span></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=5if4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5if4 OCA], [https://pdbe.org/5if4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5if4 RCSB], [https://www.ebi.ac.uk/pdbsum/5if4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5if4 ProSAT]</span></td></tr>
</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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Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade, poor survival, and resistance to chemotherapy. Mcl-1 is amplified in many human cancers, and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus, Mcl-1 is a promising cancer target. Here, we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation, mitochondrial depolarization, and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors. PDB ID CODES: Comp. 2: 5IEZ; Comp. 5: 5IF4.
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Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors.,Lee T, Bian Z, Zhao B, Hogdal LJ, Sensintaffar JL, Goodwin CM, Belmar J, Shaw S, Tarr JC, Veerasamy N, Matulis SM, Koss B, Fischer MA, Arnold AL, Camper DV, Browning CF, Rossanese OW, Budhraja A, Opferman J, Boise LH, Savona MR, Letai A, Olejniczak ET, Fesik SW FEBS Lett. 2017 Jan;591(1):240-251. doi: 10.1002/1873-3468.12497. Epub 2016 Dec, 19. PMID:27878989<ref>PMID:27878989</ref>
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==See Also==
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*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
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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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<div class="pdbe-citations 5if4" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Zhao, B]]
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[[Category: Homo sapiens]]
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[[Category: Apoptosis]]
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[[Category: Large Structures]]
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[[Category: Apoptosis-apoptosis inhibitor complex]]
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[[Category: Zhao B]]
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[[Category: Bcl-2]]
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[[Category: Myeloid cell leukemia-1]]
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Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) inhibitors using Structure-Based Design

PDB ID 5if4

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