View source for 6zie


==Crystal structure of MCL-1 in complex with a neutralizing Alphabody CMPX-383B==
<StructureSection load='6zie' size='340' side='right'caption='[[6zie]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6zie]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZIE 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6zie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zie OCA], [https://pdbe.org/6zie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zie RCSB], [https://www.ebi.ac.uk/pdbsum/6zie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zie ProSAT]</span></td></tr>
</table>
== Function ==
[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 ==
The therapeutic scope of antibody and nonantibody protein scaffolds is still prohibitively limited against intracellular drug targets. Here, we demonstrate that the Alphabody scaffold can be engineered into a cell-penetrating protein antagonist against induced myeloid leukemia cell differentiation protein MCL-1, an intracellular target in cancer, by grafting the critical B-cell lymphoma 2 homology 3 helix of MCL-1 onto the Alphabody and tagging the scaffold's termini with designed cell-penetration polypeptides. Introduction of an albumin-binding moiety extended the serum half-life of the engineered Alphabody to therapeutically relevant levels, and administration thereof in mouse tumor xenografts based on myeloma cell lines reduced tumor burden. Crystal structures of such a designed Alphabody in complex with MCL-1 and serum albumin provided the structural blueprint of the applied design principles. Collectively, we provide proof of concept for the use of Alphabodies against intracellular disease mediators, which, to date, have remained in the realm of small-molecule therapeutics.

Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting.,Pannecoucke E, Van Trimpont M, Desmet J, Pieters T, Reunes L, Demoen L, Vuylsteke M, Loverix S, Vandenbroucke K, Alard P, Henderikx P, Deroo S, Baatz F, Lorent E, Thiolloy S, Somers K, McGrath Y, Van Vlierberghe P, Lasters I, Savvides SN Sci Adv. 2021 Mar 26;7(13):eabe1682. doi: 10.1126/sciadv.abe1682. Print 2021 Mar. PMID:33771865<ref>PMID:33771865</ref>

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

==See Also==
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Desmet J]]
[[Category: Lasters I]]
[[Category: Pannecoucke E]]
[[Category: Savvides SN]]