View source for 8uky


==Crystal structure of BAK in complex with inhibiting antibody 14G6==
<StructureSection load='8uky' size='340' side='right'caption='[[8uky]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8uky]] is a 6 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=8UKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UKY 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]] 2.398&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=144:TRIS-HYDROXYMETHYL-METHYL-AMMONIUM'>144</scene>, <scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CCN:ACETONITRILE'>CCN</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8uky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uky OCA], [https://pdbe.org/8uky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uky RCSB], [https://www.ebi.ac.uk/pdbsum/8uky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uky ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BAX and BAK are pro-apoptotic members of the BCL2 family that are required to permeabilize the mitochondrial outer membrane. The proteins can adopt a non-activated monomeric conformation, or an activated conformation in which the exposed BH3 domain facilitates binding either to a prosurvival protein or to another activated BAK or BAX protein to promote pore formation. Certain cancer cells are proposed to have high levels of activated BAK sequestered by MCL1 or BCLX(L), thus priming these cells to undergo apoptosis in response to BH3 mimetic compounds that target MCL1 or BCLX(L). Here we report the first antibody, 14G6, that is specific for the non-activated BAK conformer. A crystal structure of 14G6 Fab bound to BAK revealed a binding site encompassing both the alpha1 helix and alpha5-alpha6 hinge regions of BAK, two sites involved in the unfolding of BAK during its activation. In mitochondrial experiments, 14G6 inhibited BAK unfolding triggered by three diverse BAK activators, supporting crucial roles for both alpha1 dissociation and separation of the core (alpha2-alpha5) and latch (alpha6-alpha9) regions in BAK activation. 14G6 bound the majority of BAK in several leukaemia cell lines, and binding decreased following treatment with BH3 mimetics, indicating only minor levels of constitutively activated BAK in those cells. In summary, 14G6 provides a new means of assessing BAK status in response to anti-cancer treatments.

A novel inhibitory BAK antibody enables assessment of non-activated BAK in cancer cells.,Subas Satish HP, Iyer S, Shi MX, Wong AW, Fischer KC, Wardak AZ, Lio D, Brouwer JM, Uren RT, Czabotar PE, Miller MS, Kluck RM Cell Death Differ. 2024 Jun;31(6):711-721. doi: 10.1038/s41418-024-01289-3. Epub , 2024 Apr 6. PMID:38582955<ref>PMID:38582955</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8uky" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Czabotar PE]]
[[Category: Miller MS]]