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- | [[Image:2fp3.gif|left|200px]] | |
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- | {{Structure
| + | ==Crystal structure of the Drosophila initiator caspase Dronc== |
- | |PDB= 2fp3 |SIZE=350|CAPTION= <scene name='initialview01'>2fp3</scene>, resolution 2.5Å
| + | <StructureSection load='2fp3' size='340' side='right'caption='[[2fp3]], [[Resolution|resolution]] 2.50Å' scene=''> |
- | |SITE=
| + | == Structural highlights == |
- | |LIGAND=
| + | <table><tr><td colspan='2'>[[2fp3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FP3 FirstGlance]. <br> |
- | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
- | |GENE= Nc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster]) | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fp3 OCA], [https://pdbe.org/2fp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fp3 RCSB], [https://www.ebi.ac.uk/pdbsum/2fp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fp3 ProSAT]</span></td></tr> |
- | }}
| + | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/DRONC_DROME DRONC_DROME] Involved in the activation cascade of caspases responsible for apoptosis execution. Effector of steroid-mediated apoptosis during insect metamorphosis. Overexpression promotes programmed cell death. Interaction with Diap1 is required to suppress Dronc-mediated cell death; via Diap1-mediated ubiquitination of Dronc. Rate-limiting caspase in rpr and hid death pathway.<ref>PMID:10200258</ref> <ref>PMID:10675329</ref> <ref>PMID:10984473</ref> <ref>PMID:14517550</ref> |
| + | == Evolutionary Conservation == |
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> |
| + | <jmolCheckbox> |
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fp/2fp3_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| + | </jmolCheckbox> |
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fp3 ConSurf]. |
| + | <div style="clear:both"></div> |
| | | |
- | '''Crystal structure of the Drosophila initiator caspase Dronc'''
| + | ==See Also== |
- | | + | *[[Caspase 3D structures|Caspase 3D structures]] |
- | | + | == References == |
- | ==Overview== | + | <references/> |
- | Activation of an initiator caspase is essential to the execution of apoptosis. The molecular mechanisms by which initiator caspases are activated remain poorly understood. Here we demonstrate that the autocatalytic cleavage of Dronc, an important initiator caspase in Drosophila, results in a drastic enhancement of its catalytic activity in vitro. The autocleaved Dronc forms a homodimer, whereas the uncleaved Dronc zymogen exists exclusively as a monomer. Thus the autocatalytic cleavage in Dronc induces its stable dimerization, which presumably allows the two adjacent monomers to mutually stabilize their active sites, leading to activation. Crystal structure of a prodomain-deleted Dronc zymogen, determined at 2.5 A resolution, reveals an unproductive conformation at the active site, which is consistent with the observation that the zymogen remains catalytically inactive. This study revealed insights into mechanism of Dronc activation, and in conjunction with other observations, suggests diverse mechanisms for the activation of initiator caspases.
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure==
| + | |
- | 2FP3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FP3 OCA].
| + | |
- | | + | |
- | ==Reference== | + | |
- | Structure and activation mechanism of the Drosophila initiator caspase Dronc., Yan N, Huh JR, Schirf V, Demeler B, Hay BA, Shi Y, J Biol Chem. 2006 Mar 31;281(13):8667-74. Epub 2006 Jan 30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16446367 16446367]
| + | |
| [[Category: Drosophila melanogaster]] | | [[Category: Drosophila melanogaster]] |
- | [[Category: Single protein]] | + | [[Category: Large Structures]] |
- | [[Category: Gu, L.]] | + | [[Category: Gu L]] |
- | [[Category: Shi, Y.]] | + | [[Category: Shi Y]] |
- | [[Category: Yan, N.]] | + | [[Category: Yan N]] |
- | [[Category: active site conformation]]
| + | |
- | [[Category: apoptosis]]
| + | |
- | [[Category: caspase]]
| + | |
- | [[Category: dimerization]]
| + | |
- | [[Category: initiator caspase activation]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:55:07 2008''
| + | |
| Structural highlights
Function
DRONC_DROME Involved in the activation cascade of caspases responsible for apoptosis execution. Effector of steroid-mediated apoptosis during insect metamorphosis. Overexpression promotes programmed cell death. Interaction with Diap1 is required to suppress Dronc-mediated cell death; via Diap1-mediated ubiquitination of Dronc. Rate-limiting caspase in rpr and hid death pathway.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Dorstyn L, Colussi PA, Quinn LM, Richardson H, Kumar S. DRONC, an ecdysone-inducible Drosophila caspase. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4307-12. PMID:10200258
- ↑ Meier P, Silke J, Leevers SJ, Evan GI. The Drosophila caspase DRONC is regulated by DIAP1. EMBO J. 2000 Feb 15;19(4):598-611. PMID:10675329 doi:http://dx.doi.org/10.1093/emboj/19.4.598
- ↑ Quinn LM, Dorstyn L, Mills K, Colussi PA, Chen P, Coombe M, Abrams J, Kumar S, Richardson H. An essential role for the caspase dronc in developmentally programmed cell death in Drosophila. J Biol Chem. 2000 Dec 22;275(51):40416-24. PMID:10984473 doi:http://dx.doi.org/10.1074/jbc.M002935200
- ↑ Chai J, Yan N, Huh JR, Wu JW, Li W, Hay BA, Shi Y. Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nat Struct Biol. 2003 Nov;10(11):892-8. Epub 2003 Sep 28. PMID:14517550 doi:10.1038/nsb989
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