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==Crystal structure of the Drosophila initiator caspase Dronc==
==Crystal structure of the Drosophila initiator caspase Dronc==
<StructureSection load='2fp3' size='340' side='right' caption='[[2fp3]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='2fp3' size='340' side='right'caption='[[2fp3]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2fp3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FP3 FirstGlance]. <br>
<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>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</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]] 2.5&#8491;</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=2fp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fp3 OCA], [http://pdbe.org/2fp3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fp3 RCSB], [http://www.ebi.ac.uk/pdbsum/2fp3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fp3 ProSAT]</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=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>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/ICENC_DROME ICENC_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 th is required to suppress Nc-mediated cell death; via th-mediated ubiquitination of Nc. Rate-limiting caspase in rpr and W death pathway.<ref>PMID:10200258</ref> <ref>PMID:10675329</ref> <ref>PMID:10984473</ref> <ref>PMID:14517550</ref>
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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].
</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>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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:16446367<ref>PMID:16446367</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2fp3" 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: Drome]]
[[Category: Drosophila melanogaster]]
[[Category: Gu, L]]
[[Category: Large Structures]]
[[Category: Shi, Y]]
[[Category: Gu L]]
[[Category: Yan, N]]
[[Category: Shi Y]]
[[Category: Active site conformation]]
[[Category: Yan N]]
[[Category: Apoptosis]]
[[Category: Caspase]]
[[Category: Dimerization]]
[[Category: Hydrolysis-apoptosis complex]]
[[Category: Initiator caspase activation]]

Latest revision as of 12:24, 14 February 2024

Crystal structure of the Drosophila initiator caspase DroncCrystal structure of the Drosophila initiator caspase Dronc

Structural highlights

2fp3 is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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

2fp3, resolution 2.50Å

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