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| | ==Caspase-7 in Complex with DARPin C7_16== | | ==Caspase-7 in Complex with DARPin C7_16== |
| - | <StructureSection load='4jb8' size='340' side='right' caption='[[4jb8]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4jb8' size='340' side='right'caption='[[4jb8]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jb8]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JB8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JB8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jb8]] is a 3 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=4JB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JB8 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ibc|3ibc]], [[4j92|4j92]]</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]] 1.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP7, MCH3 ([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=4jb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jb8 OCA], [https://pdbe.org/4jb8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jb8 RCSB], [https://www.ebi.ac.uk/pdbsum/4jb8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jb8 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-7 Caspase-7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.60 3.4.22.60] </span></td></tr>
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| - | <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=4jb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jb8 OCA], [http://pdbe.org/4jb8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jb8 RCSB], [http://www.ebi.ac.uk/pdbsum/4jb8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jb8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CASP7_HUMAN CASP7_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. | + | [https://www.uniprot.org/uniprot/CASP7_HUMAN CASP7_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Caspase|Caspase]] | + | *[[Caspase 3D structures|Caspase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caspase-7]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Fluetsch, A]] | + | [[Category: Fluetsch A]] |
| - | [[Category: Gruetter, M G]] | + | [[Category: Gruetter MG]] |
| - | [[Category: Seeger, M A]] | + | [[Category: Seeger MA]] |
| - | [[Category: Complex structure]]
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| - | [[Category: Hydrolase-de novo protein complex]]
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| - | [[Category: Selected darpin c7_16]]
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| Structural highlights
Function
CASP7_HUMAN Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death.
Publication Abstract from PubMed
Designed ankyrin repeat proteins (DARPins) are well-established binding molecules based on a highly stable nonantibody scaffold. Building on 13 crystal structures of DARPin-target complexes and stability measurements of DARPin mutants, we have generated a new DARPin library containing an extended randomized surface. To counteract the enrichment of unspecific hydrophobic binders during selections against difficult targets containing hydrophobic surfaces such as membrane proteins, the frequency of apolar residues at diversified positions was drastically reduced and substituted by an increased number of tyrosines. Ribosome display selections against two human caspases and membrane transporter AcrB yielded highly enriched pools of unique and strong DARPin binders which were mainly monomeric. We noted a prominent enrichment of tryptophan residues during binder selections. A crystal structure of a representative of this library in complex with caspase-7 visualizes the key roles of both tryptophans and tyrosines in providing target contacts. These aromatic and polar side chains thus substitute the apolar residues valine, leucine, isoleucine, methionine, and phenylalanine of the original DARPins. Our work describes biophysical and structural analyses required to extend existing binder scaffolds and simplifies an existing protocol for the assembly of highly diverse synthetic binder libraries.
Design, construction, and characterization of a second-generation DARPin library with reduced hydrophobicity.,Seeger MA, Zbinden R, Flutsch A, Gutte PG, Engeler S, Roschitzki-Voser H, Grutter MG Protein Sci. 2013 Jul 19. doi: 10.1002/pro.2312. PMID:23868333[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Seeger MA, Zbinden R, Flutsch A, Gutte PG, Engeler S, Roschitzki-Voser H, Grutter MG. Design, construction, and characterization of a second-generation DARPin library with reduced hydrophobicity. Protein Sci. 2013 Jul 19. doi: 10.1002/pro.2312. PMID:23868333 doi:10.1002/pro.2312
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