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| - | ==CASPASE-3:CAS60254719== | + | |
| - | <StructureSection load='2xyh' size='340' side='right' caption='[[2xyh]], [[Resolution|resolution]] 1.89Å' scene=''> | + | ==Caspase-3:CAS60254719== |
| | + | <StructureSection load='2xyh' size='340' side='right'caption='[[2xyh]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xyh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XYH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XYH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2xyh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XYH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TQ9:5-CHLORO-4-OXOPENTANOIC+ACID'>TQ9</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]] 1.89Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nme|1nme]], [[1rhk|1rhk]], [[2j33|2j33]], [[1rhr|1rhr]], [[1nms|1nms]], [[1nmq|1nmq]], [[1rhq|1rhq]], [[1rhj|1rhj]], [[2cnn|2cnn]], [[2dko|2dko]], [[2c2k|2c2k]], [[2cjy|2cjy]], [[2j31|2j31]], [[2cnl|2cnl]], [[2c2m|2c2m]], [[2cnk|2cnk]], [[1cp3|1cp3]], [[2cjx|2cjx]], [[1re1|1re1]], [[2j30|2j30]], [[2xyg|2xyg]], [[2c1e|2c1e]], [[1pau|1pau]], [[2cdr|2cdr]], [[2j32|2j32]], [[1i3o|1i3o]], [[2cno|2cno]], [[1gfw|1gfw]], [[1rhu|1rhu]], [[1rhm|1rhm]], [[2c2o|2c2o]], [[1qx3|1qx3]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TQ9:5-CHLORO-4-OXOPENTANOIC+ACID'>TQ9</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-3 Caspase-3], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.56 3.4.22.56] </span></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=2xyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xyh OCA], [https://pdbe.org/2xyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xyh RCSB], [https://www.ebi.ac.uk/pdbsum/2xyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xyh 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=2xyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xyh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xyh RCSB], [http://www.ebi.ac.uk/pdbsum/2xyh PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</ref> | + | [https://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2xyh" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Caspase|Caspase]] | + | *[[Caspase 3D structures|Caspase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caspase-3]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Ganesan, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Grutter, M G]] | + | [[Category: Ganesan R]] |
| - | [[Category: Jelakovic, S]]
| + | [[Category: Grutter MG]] |
| - | [[Category: Mittl, P R]]
| + | [[Category: Jelakovic S]] |
| - | [[Category: Apoptosis]] | + | [[Category: Mittl PR]] |
| - | [[Category: Docking]] | + | |
| - | [[Category: Hydrolase]] | + | |
| - | [[Category: In silico screening]]
| + | |
| Structural highlights
Function
CASP3_HUMAN Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.[1] [2]
Publication Abstract from PubMed
Using a fragment-based docking procedure, several small-molecule inhibitors of caspase-3 were identified and tested and the crystal structures of three inhibitor complexes were determined. The crystal structures revealed that one inhibitor (NSC 18508) occupies only the S1 subsite, while two other inhibitors (NSC 89167 and NSC 251810) bind only to the prime part of the substrate-binding site. One of the major conformational changes observed in all three caspase-3-inhibitor complexes is a rotation of the Tyr204 side chain, which blocks the S2 subsite. In addition, the structural variability of the residues shaping the S1-S4 as well as the S1' subsites supports an induced-fit mechanism for the binding of the inhibitors in the active site. The high-resolution crystal structures reported here provide novel insights into the architecture of the substrate-binding site, which might be useful for the design of more potent caspase inhibitors.
In silico identification and crystal structure validation of caspase-3 inhibitors without a P1 aspartic acid moiety.,Ganesan R, Jelakovic S, Mittl PR, Caflisch A, Grutter MG Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Aug 1;67(Pt, 8):842-50. Epub 2011 Jul 13. PMID:21821879[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, et al.. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37-43. PMID:7596430 doi:http://dx.doi.org/10.1038/376037a0
- ↑ Cabrera JR, Bouzas-Rodriguez J, Tauszig-Delamasure S, Mehlen P. RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. J Biol Chem. 2011 Apr 22;286(16):14628-38. doi: 10.1074/jbc.M110.195461. Epub, 2011 Feb 28. PMID:21357690 doi:10.1074/jbc.M110.195461
- ↑ Ganesan R, Jelakovic S, Mittl PR, Caflisch A, Grutter MG. In silico identification and crystal structure validation of caspase-3 inhibitors without a P1 aspartic acid moiety. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Aug 1;67(Pt, 8):842-50. Epub 2011 Jul 13. PMID:21821879 doi:10.1107/S1744309111018604
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