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3spf

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Current revision (09:54, 1 March 2024) (edit) (undo)
 
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<StructureSection load='3spf' size='340' side='right'caption='[[3spf]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
<StructureSection load='3spf' size='340' side='right'caption='[[3spf]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3spf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3spf]] is a 1 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.7&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3sp7|3sp7]]</div></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=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([https://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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [https://pdbe.org/3spf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [https://www.ebi.ac.uk/pdbsum/3spf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf ProSAT]</span></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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [https://pdbe.org/3spf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [https://www.ebi.ac.uk/pdbsum/3spf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN]] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref> Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>
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[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref> Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Employing a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of the anti-apoptotic proteins Bcl-2 and Bcl-xL. An initial lead compound with a new scaffold was designed based upon the crystal structure of Bcl-xL and U.S. Food and Drug Administration (FDA) approved drugs and was found to have an affinity of 100 muM for both Bcl-2 and Bcl-xL. Linking this weak lead to another weak-affinity fragment derived from Abbott's ABT-737 led to an improvement of the binding affinity by a factor of &gt;10 000. Further optimization ultimately yielded compounds with subnanomolar binding affinities for both Bcl-2 and Bcl-xL and potent cellular activity. The best compound (21) binds to Bcl-xL and Bcl-2 with K(i) &lt; 1 nM, inhibits cell growth in the H146 and H1417 small-cell lung cancer cell lines with IC(50) values of 60-90 nM, and induces robust cell death in the H146 cancer cell line at 30-100 nM.
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Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold.,Zhou H, Chen J, Meagher JL, Yang CY, Aguilar A, Liu L, Bai L, Cong X, Cai Q, Fang X, Stuckey JA, Wang S J Med Chem. 2012 May 24;55(10):4664-82. Epub 2012 May 10. PMID:22448988<ref>PMID:22448988</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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<div class="pdbe-citations 3spf" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Meagher, J L]]
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[[Category: Meagher JL]]
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[[Category: Stuckey, J A]]
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[[Category: Stuckey JA]]
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[[Category: Apoptosis regulator-inhibitor complex]]
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[[Category: Apoptosis-apoptosis inhibitor complex]]
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[[Category: Bcl-2-like protein]]
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Current revision

Crystal Structure of Bcl-xL bound to BM501

PDB ID 3spf

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