5uup: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 5uup is ~~ON HOLD until Paper~~ Publication

==Human Bfl-1 covalently cross-linked to an electrophilic variant of a Bfl-1-specific selected peptide==

== Structural highlights ==

<table><tr><td colspan='2'>[[5uup]] 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=5UUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UUP 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]] 1.726Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=5uup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uup OCA], [https://pdbe.org/5uup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uup RCSB], [https://www.ebi.ac.uk/pdbsum/5uup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uup ProSAT]</span></td></tr>

</table>

== Function ==

[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).

== Publication Abstract from PubMed ==

Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs. High-resolution crystal structures show that designed peptide FS2 binds Bfl-1 in a shifted geometry, relative to PUMA and other binding partners, due to a set of epistatic mutations. FS2 modified with an electrophile reacts with a cysteine near the peptide-binding groove to augment specificity. Designed Bfl-1 binders provide reagents for cellular profiling and leads for developing enhanced and cell-permeable peptide or small-molecule inhibitors.

~~Authors~~:

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1.,Jenson JM, Ryan JA, Grant RA, Letai A, Keating AE Elife. 2017 Jun 8;6. pii: e25541. doi: 10.7554/eLife.25541. PMID:28594323<ref>PMID:28594323</ref>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

==See Also==

*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Synthetic construct]]

[[Category: Grant RA]]

[[Category: Jenson JM]]

[[Category: Keating AE]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5uup is ON HOLD  until Paper Publication
+==Human Bfl-1 covalently cross-linked to an electrophilic variant of a Bfl-1-specific selected peptide==
+<StructureSection load='5uup' size='340' side='right'caption='[[5uup]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5uup]] 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=5UUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UUP 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]] 1.726&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=5uup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uup OCA], [https://pdbe.org/5uup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uup RCSB], [https://www.ebi.ac.uk/pdbsum/5uup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uup ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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;">
+== Publication Abstract from PubMed ==
+Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are &gt; 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs. High-resolution crystal structures show that designed peptide FS2 binds Bfl-1 in a shifted geometry, relative to PUMA and other binding partners, due to a set of epistatic mutations. FS2 modified with an electrophile reacts with a cysteine near the peptide-binding groove to augment specificity. Designed Bfl-1 binders provide reagents for cellular profiling and leads for developing enhanced and cell-permeable peptide or small-molecule inhibitors.
-Authors:
+Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1.,Jenson JM, Ryan JA, Grant RA, Letai A, Keating AE Elife. 2017 Jun 8;6. pii: e25541. doi: 10.7554/eLife.25541. PMID:28594323<ref>PMID:28594323</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5uup" 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: Grant RA]]
+[[Category: Jenson JM]]
+[[Category: Keating AE]]