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| | <StructureSection load='5jft' size='340' side='right'caption='[[5jft]], [[Resolution|resolution]] 2.28Å' scene=''> | | <StructureSection load='5jft' size='340' side='right'caption='[[5jft]], [[Resolution|resolution]] 2.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jft]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JFT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JFT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jft]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Unidentified_'CNM-group'_bacterium_HXN600 Unidentified 'CNM-group' bacterium HXN600]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JFT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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]] 2.28Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">casp3a, casp3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=5jft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jft OCA], [https://pdbe.org/5jft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jft RCSB], [https://www.ebi.ac.uk/pdbsum/5jft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jft ProSAT]</span></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=5jft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jft OCA], [http://pdbe.org/5jft PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jft RCSB], [http://www.ebi.ac.uk/pdbsum/5jft PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jft ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A2R8QUC0_DANRE A0A2R8QUC0_DANRE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | |
| - | [[Category: Large Structures]] | |
| - | [[Category: Clark, A C]] | |
| - | [[Category: Dirscherl, H]] | |
| - | [[Category: Hamilton, P T]] | |
| - | [[Category: MacKenzie, S H]] | |
| - | [[Category: Maciag, J J]] | |
| - | [[Category: Swartz, P D]] | |
| - | [[Category: Tucker, M B]] | |
| - | [[Category: Yoder, J A]] | |
| - | [[Category: Apoptosis]] | |
| | [[Category: Danio rerio]] | | [[Category: Danio rerio]] |
| - | [[Category: Hydrolase]] | + | [[Category: Large Structures]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]] | + | [[Category: Unidentified 'CNM-group' bacterium HXN600]] |
| - | [[Category: Phage display substrate library]] | + | [[Category: Clark AC]] |
| - | [[Category: Substrate recognition]] | + | [[Category: Dirscherl H]] |
| | + | [[Category: Hamilton PT]] |
| | + | [[Category: MacKenzie SH]] |
| | + | [[Category: Maciag JJ]] |
| | + | [[Category: Swartz PD]] |
| | + | [[Category: Tucker MB]] |
| | + | [[Category: Yoder JA]] |
| Structural highlights
Function
A0A2R8QUC0_DANRE
Publication Abstract from PubMed
The regulation of caspase-3 enzyme activity is a vital process in cell fate decisions leading to cell differentiation and tissue development or to apoptosis. The zebrafish, Danio rerio, has become an increasingly popular animal model to study several human diseases because of their transparent embryos, short reproductive cycles, and ease of drug administration. While apoptosis is an evolutionarily conserved process in metazoans, little is known about caspases from zebrafish, particularly regarding substrate specificity and allosteric regulation compared to the human caspases. We cloned zebrafish caspase-3a (casp3a) and examined substrate specificity of the recombinant protein, Casp3a, compared to human caspase-3 (CASP3) by utilizing M13 bacteriophage substrate libraries that incorporated either random amino acids at P5-P1' or aspartate fixed at P1. The results show a preference for the tetrapeptide sequence DNLD for both enzymes, but the P4 position of zebrafish Casp3a also accommodates valine equally well. We determined the structure of zebrafish Casp3a to 2.28A resolution by X-ray crystallography, and when combined with molecular dynamics simulations, the results suggest that a limited number of amino acid substitutions near the active site result in plasticity of the S4 sub-site by increasing flexibility of one active site loop and by affecting hydrogen-bonding with substrate. The data show that zebrafish Casp3a exhibits a broader substrate portfolio, suggesting overlap with the functions of caspase-6 in zebrafish development.
Phage display and structural studies reveal plasticity in substrate specificity of caspase-3a from zebrafish.,Tucker MB, MacKenzie SH, Maciag JJ, Dirscherl Ackerman H, Swartz P, Yoder JA, Hamilton PT, Clay Clark A Protein Sci. 2016 Nov;25(11):2076-2088. doi: 10.1002/pro.3032. Epub 2016 Sep 14. PMID:27577093[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tucker MB, MacKenzie SH, Maciag JJ, Dirscherl Ackerman H, Swartz P, Yoder JA, Hamilton PT, Clay Clark A. Phage display and structural studies reveal plasticity in substrate specificity of caspase-3a from zebrafish. Protein Sci. 2016 Nov;25(11):2076-2088. doi: 10.1002/pro.3032. Epub 2016 Sep 14. PMID:27577093 doi:http://dx.doi.org/10.1002/pro.3032
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