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5iez

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Revision as of 13:49, 30 August 2023

Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) inhibitors using Structure-Based Design

Structural highlights

5iez is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

Publication Abstract from PubMed

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bingle CD, Craig RW, Swales BM, Singleton V, Zhou P, Whyte MK. Exon skipping in Mcl-1 results in a bcl-2 homology domain 3 only gene product that promotes cell death. J Biol Chem. 2000 Jul 21;275(29):22136-46. PMID:10766760 doi:10.1074/jbc.M909572199
↑ 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. Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors. FEBS Lett. 2017 Jan;591(1):240-251. doi: 10.1002/1873-3468.12497. Epub 2016 Dec, 19. PMID:27878989 doi:http://dx.doi.org/10.1002/1873-3468.12497

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5iez"

Categories: Homo sapiens | Large Structures | Zhao B

@@ Line 3: / Line 3: @@
 <StructureSection load='5iez' size='340' side='right'caption='[[5iez]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5iez]] is a 4 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=5IEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IEZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5iez]] is a 4 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=5IEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IEZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6AL:3-({6-CHLORO-3-[3-(4-CHLORO-3,5-DIMETHYLPHENOXY)PROPYL]-7-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)-1H-INDOLE-2-CARBONYL}AMINO)BENZOIC+ACID'>6AL</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]] 2.6&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5if4|5if4]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6AL:3-({6-CHLORO-3-[3-(4-CHLORO-3,5-DIMETHYLPHENOXY)PROPYL]-7-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)-1H-INDOLE-2-CARBONYL}AMINO)BENZOIC+ACID'>6AL</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=5iez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iez OCA], [https://pdbe.org/5iez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iez RCSB], [https://www.ebi.ac.uk/pdbsum/5iez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iez 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=5iez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iez OCA], [http://pdbe.org/5iez PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iez RCSB], [http://www.ebi.ac.uk/pdbsum/5iez PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iez ProSAT]</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>
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Zhao, B]]
+[[Category: Zhao B]]
-[[Category: Apoptosis]]
-[[Category: Apoptosis-apoptosis inhibitor complex]]
-[[Category: Bcl-2]]
-[[Category: Myeloid cell leukemia-1]]

5iez

From Proteopedia

Revision as of 13:49, 30 August 2023

Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) inhibitors using Structure-Based Design

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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