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2xzd

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Revision as of 12:27, 22 July 2020

Caspase-3 in Complex with an Inhibitory DARPin-3.4

Structural highlights

2xzd is a 6 chain structure with sequence from Human and Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	1rhk, 1rhq, 2dko, 2xyp, 2cjy, 2j31, 2xyh, 2cjx, 1re1, 2xyg, 2c1e, 2cno, 1gfw, 1qx3, 1rhm, 1nme, 2j33, 1rhr, 1nms, 1nmq, 1rhj, 2cnn, 2c2k, 2cnl, 2c2m, 1cp3, 2cnk, 2j30, 1pau, 2cdr, 2j32, 1i3o, 1rhu, 2c2o
Activity:	Caspase-3, with EC number 3.4.22.56
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Dysregulation of apoptosis is associated with several human diseases. The main apoptotic mediators are caspases, which propagate death signals to downstream targets. Executioner caspase-3 is responsible for the majority of cleavage events and its therapeutic potential is of high interest with to date several available active site peptide inhibitors. These molecules inhibit caspase-3, but also homologous caspases. Here, we describe caspase-3 specific inhibitors D3.4 and D3.8, which have been selected from a library of designed ankyrin repeat proteins (DARPins). The crystal structures of D3.4 and mutants thereof show how high specificity and inhibition is achieved. They also show similarities in the binding mode with that of the natural caspase inhibitor XIAP (X-linked inhibitor of apoptosis). The kinetic data reveal a competitive inhibition mechanism. D3.4 is specific for caspase-3 and does not bind the highly homologous caspase-7. D3.4 therefore is an excellent tool to define the precise role of caspase-3 in the various apoptotic pathways.

Specific Inhibition of Caspase-3 by a Competitive DARPin: Molecular Mimicry between Native and Designed Inhibitors.,Schroeder T, Barandun J, Flutsch A, Briand C, Mittl PR, Grutter MG Structure. 2013 Jan 15. pii: S0969-2126(12)00466-2. doi:, 10.1016/j.str.2012.12.011. PMID:23333429^[3]

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

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
↑ Schroeder T, Barandun J, Flutsch A, Briand C, Mittl PR, Grutter MG. Specific Inhibition of Caspase-3 by a Competitive DARPin: Molecular Mimicry between Native and Designed Inhibitors. Structure. 2013 Jan 15. pii: S0969-2126(12)00466-2. doi:, 10.1016/j.str.2012.12.011. PMID:23333429 doi:http://dx.doi.org/10.1016/j.str.2012.12.011

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2xzd"

@@ Line 1: / Line 1: @@
 ==Caspase-3 in Complex with an Inhibitory DARPin-3.4==
-<StructureSection load='2xzd' size='340' side='right' caption='[[2xzd]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='2xzd' size='340' side='right'caption='[[2xzd]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xzd]] is a 6 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=2XZD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XZD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xzd]] is a 6 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=2XZD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XZD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rhk|1rhk]], [[1rhq|1rhq]], [[2dko|2dko]], [[2xyp|2xyp]], [[2cjy|2cjy]], [[2j31|2j31]], [[2xyh|2xyh]], [[2cjx|2cjx]], [[1re1|1re1]], [[2xyg|2xyg]], [[2c1e|2c1e]], [[2cno|2cno]], [[1gfw|1gfw]], [[1qx3|1qx3]], [[1rhm|1rhm]], [[1nme|1nme]], [[2j33|2j33]], [[1rhr|1rhr]], [[1nms|1nms]], [[1nmq|1nmq]], [[1rhj|1rhj]], [[2cnn|2cnn]], [[2c2k|2c2k]], [[2cnl|2cnl]], [[2c2m|2c2m]], [[1cp3|1cp3]], [[2cnk|2cnk]], [[2j30|2j30]], [[1pau|1pau]], [[2cdr|2cdr]], [[2j32|2j32]], [[1i3o|1i3o]], [[1rhu|1rhu]], [[2c2o|2c2o]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xzd OCA], [http://pdbe.org/2xzd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xzd RCSB], [http://www.ebi.ac.uk/pdbsum/2xzd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xzd 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=2xzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xzd OCA], [http://pdbe.org/2xzd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xzd RCSB], [http://www.ebi.ac.uk/pdbsum/2xzd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xzd ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 23: @@
 ==See Also==
-*[[Caspase|Caspase]]
+*[[Caspase 3D structures|Caspase 3D structures]]
 == References ==
 <references/>
@@ Line 30: / Line 30: @@
 [[Category: Caspase-3]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Synthetic construct sequences]]
 [[Category: Barandun, J]]

2xzd

From Proteopedia

Revision as of 12:27, 22 July 2020

Caspase-3 in Complex with an Inhibitory DARPin-3.4

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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