6vo4: Difference between revisions
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==Crystal Structure Analysis of BFL1== | ==Crystal Structure Analysis of BFL1== | ||
<StructureSection load='6vo4' size='340' side='right'caption='[[6vo4]]' scene=''> | <StructureSection load='6vo4' size='340' side='right'caption='[[6vo4]], [[Resolution|resolution]] 1.74Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VO4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VO4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6vo4]] is a 1 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=6VO4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VO4 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vo4 OCA], [http://pdbe.org/6vo4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vo4 RCSB], [http://www.ebi.ac.uk/pdbsum/6vo4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vo4 ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCL2A1, BCL2L5, BFL1, GRS, HBPA1 ([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'>[http://proteopedia.org/fgij/fg.htm?mol=6vo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vo4 OCA], [http://pdbe.org/6vo4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vo4 RCSB], [http://www.ebi.ac.uk/pdbsum/6vo4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vo4 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/B2LA1_HUMAN B2LA1_HUMAN]] Retards apoptosis induced by IL-3 deprivation. May function in the response of hemopoietic cells to external signals and in maintaining endothelial survival during infection (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The BCL-2 family is composed of anti- and pro-apoptotic members that respectively protect or disrupt mitochondrial integrity. Anti-apoptotic overexpression can promote oncogenesis by trapping the BCL-2 homology 3 (BH3) "killer domains" of pro-apoptotic proteins in a surface groove, blocking apoptosis. Groove inhibitors, such as the relatively large BCL-2 drug venetoclax (868 Da), have emerged as cancer therapies. BFL-1 remains an undrugged oncogenic protein and can cause venetoclax resistance. Having identified a unique C55 residue in the BFL-1 groove, we performed a disulfide tethering screen to determine if C55 reactivity could enable smaller molecules to block BFL-1's BH3-binding functionality. We found that a disulfide-bearing N-acetyltryptophan analog (304 Da adduct) effectively targeted BFL-1 C55 and reversed BFL-1-mediated suppression of mitochondrial apoptosis. Structural analyses implicated the conserved leucine-binding pocket of BFL-1 as the interaction site, resulting in conformational remodeling. Thus, therapeutic targeting of BFL-1 may be achievable through the design of small, cysteine-reactive drugs. | |||
Identification of a Covalent Molecular Inhibitor of Anti-apoptotic BFL-1 by Disulfide Tethering.,Harvey EP, Hauseman ZJ, Cohen DT, Rettenmaier TJ, Lee S, Huhn AJ, Wales TE, Seo HS, Luccarelli J, Newman CE, Guerra RM, Bird GH, Dhe-Paganon S, Engen JR, Wells JA, Walensky LD Cell Chem Biol. 2020 Jun 18;27(6):647-656.e6. doi:, 10.1016/j.chembiol.2020.04.004. Epub 2020 May 14. PMID:32413285<ref>PMID:32413285</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6vo4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Seo, H- | [[Category: Dhe-Paganon, S]] | ||
[[Category: Seo, H S]] | |||
[[Category: Apoptosis]] | |||
[[Category: Bcl-2 family]] | |||
[[Category: Bfl-1/a1]] | |||
[[Category: Disulfide tethering]] | |||
[[Category: Inhibitor]] | |||
[[Category: Small molecule]] | |||
Revision as of 08:58, 20 July 2020
Crystal Structure Analysis of BFL1
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