View source for 6mcy


==Crystal structure of mouse Bak==
<StructureSection load='6mcy' size='340' side='right'caption='[[6mcy]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mcy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MCY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.748&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></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=6mcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mcy OCA], [https://pdbe.org/6mcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mcy RCSB], [https://www.ebi.ac.uk/pdbsum/6mcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mcy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BAK_MOUSE BAK_MOUSE] In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Activating the intrinsic apoptosis pathway with small molecules is now a clinically validated approach to cancer therapy. In contrast, blocking apoptosis to prevent the death of healthy cells in disease settings has not been achieved. Caspases have been favored, but they act too late in apoptosis to provide long-term protection. The critical step in committing a cell to death is activation of BAK or BAX, pro-death BCL-2 proteins mediating mitochondrial damage. Apoptosis cannot proceed in their absence. Here we show that WEHI-9625, a novel tricyclic sulfone small molecule, binds to VDAC2 and promotes its ability to inhibit apoptosis driven by mouse BAK. In contrast to caspase inhibitors, WEHI-9625 blocks apoptosis before mitochondrial damage, preserving cellular function and long-term clonogenic potential. Our findings expand on the key role of VDAC2 in regulating apoptosis and demonstrate that blocking apoptosis at an early stage is both advantageous and pharmacologically tractable.

A small molecule interacts with VDAC2 to block mouse BAK-driven apoptosis.,van Delft MF, Chappaz S, Khakham Y, Bui CT, Debrincat MA, Lowes KN, Brouwer JM, Grohmann C, Sharp PP, Dagley LF, Li L, McArthur K, Luo MX, Chin HS, Fairlie WD, Lee EF, Segal D, Duflocq S, Lessene R, Bernard S, Peilleron L, Nguyen T, Miles C, Wan SS, Lane RM, Wardak A, Lackovic K, Colman PM, Sandow JJ, Webb AI, Czabotar PE, Dewson G, Watson KG, Huang DCS, Lessene G, Kile BT Nat Chem Biol. 2019 Nov;15(11):1057-1066. doi: 10.1038/s41589-019-0365-8. Epub, 2019 Oct 7. PMID:31591564<ref>PMID:31591564</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mcy" style="background-color:#fffaf0;"></div>

==See Also==
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Brouwer JM]]
[[Category: Colman PM]]
[[Category: Czabotar PE]]