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| | <StructureSection load='6e3i' size='340' side='right'caption='[[6e3i]], [[Resolution|resolution]] 1.48Å' scene=''> | | <StructureSection load='6e3i' size='340' side='right'caption='[[6e3i]], [[Resolution|resolution]] 1.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6e3i]] is a 2 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=6E3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E3I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6e3i]] 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=6E3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E3I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.481Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6e3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e3i OCA], [https://pdbe.org/6e3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e3i RCSB], [https://www.ebi.ac.uk/pdbsum/6e3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e3i ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e3i OCA], [http://pdbe.org/6e3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e3i RCSB], [http://www.ebi.ac.uk/pdbsum/6e3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e3i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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). | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6e3i" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6e3i" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jenson, J M]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Keating, A E]] | + | [[Category: Jenson JM]] |
| - | [[Category: Anti-apoptotic bcl-2]] | + | [[Category: Keating AE]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Design]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
Function
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).
Publication Abstract from PubMed
Many applications in protein engineering require optimizing multiple protein properties simultaneously, such as binding one target but not others or binding a target while maintaining stability. Such multistate design problems require navigating a high-dimensional space to find proteins with desired characteristics. A model that relates protein sequence to functional attributes can guide design to solutions that would be hard to discover via screening. In this work, we measured thousands of protein-peptide binding affinities with the high-throughput interaction assay amped SORTCERY and used the data to parameterize a model of the alpha-helical peptide-binding landscape for three members of the Bcl-2 family of proteins: Bcl-xL, Mcl-1, and Bfl-1. We applied optimization protocols to explore extremes in this landscape to discover peptides with desired interaction profiles. Computational design generated 36 peptides, all of which bound with high affinity and specificity to just one of Bcl-xL, Mcl-1, or Bfl-1, as intended. We designed additional peptides that bound selectively to two out of three of these proteins. The designed peptides were dissimilar to known Bcl-2-binding peptides, and high-resolution crystal structures confirmed that they engaged their targets as expected. Excellent results on this challenging problem demonstrate the power of a landscape modeling approach, and the designed peptides have potential uses as diagnostic tools or cancer therapeutics.
Peptide design by optimization on a data-parameterized protein interaction landscape.,Jenson JM, Xue V, Stretz L, Mandal T, Reich LL, Keating AE Proc Natl Acad Sci U S A. 2018 Oct 15. pii: 1812939115. doi:, 10.1073/pnas.1812939115. PMID:30322927[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jenson JM, Xue V, Stretz L, Mandal T, Reich LL, Keating AE. Peptide design by optimization on a data-parameterized protein interaction landscape. Proc Natl Acad Sci U S A. 2018 Oct 15. pii: 1812939115. doi:, 10.1073/pnas.1812939115. PMID:30322927 doi:http://dx.doi.org/10.1073/pnas.1812939115
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