3nr2

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Crystal structure of Caspase-6 zymogen

Structural highlights

3nr2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.9Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CASP6_HUMAN Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.

Publication Abstract from PubMed

Dimeric effectors caspase 3 and caspase 7 are activated by initiator caspase processing. In this study, we report the crystal structures of effector caspase 6 (CASP6) zymogen and N-Acetyl-Val-Glu-Ile-Asp-al-inhibited CASP6. Both of these forms of CASP6 have a dimeric structure, and in CASP6 zymogen the intersubunit cleavage site (190)TEVD(193) is well structured and inserts into the active site. This positions residue Asp 193 to be easily attacked by the catalytic residue Cys 163. We demonstrate biochemically that intramolecular cleavage at Asp 193 is a prerequisite for CASP6 self-activation and that this activation mechanism is dependent on the length of the L2 loop. Our results indicate that CASP6 can be activated and regulated through intramolecular self-cleavage.

Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation.,Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, Leblanc AC, Su XD EMBO Rep. 2010 Oct 1. PMID:20890311[1]

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

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Citations
10 reviews cite this structure
Huntington's disease: from molecular pathogenesis to clinical treatment.
Ross et al. (2011)
9 more
38 other articles
No citations found

See Also

References

  1. ↑ Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, Leblanc AC, Su XD. Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation. EMBO Rep. 2010 Oct 1. PMID:20890311 doi:10.1038/embor.2010.141

Contents


PDB ID 3nr2

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OCA

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