PDBsum entry: 1m72

Hydrolase/hydrolase inhibitor

PDB id: 1m72

Contents

Protein chains

247 a.a. *

Ligands

ACE-ASP-GLU-VAL-ASP-0QE ×3

EDO ×8

Waters ×318

* Residue conservation analysis

PDB id:

1m72

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of caspase-1 from spodoptera frugiperda

Structure:

Caspase-1. Chain: a, b, c. Engineered: yes. Ace-asp-glu-val-asp-chloromethylketone. Chain: d, e, f. Engineered: yes

Source:

Spodoptera frugiperda. Fall armyworm. Organism_taxid: 7108. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes. Other_details: the peptide is a synthetic tetrapeptide inhi

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.30Å R-factor: 0.183 R-free: 0.232

Authors:

C.M.Forsyth,D.Lemongello,P.D.Friesen,A.J.Fisher

Key ref:

C.M.Forsyth et al. (2004). Crystal structure of an invertebrate caspase. J Biol Chem, 279, 7001-7008. PubMed id: 14645217 DOI: 10.1074/jbc.M312472200

Date:

18-Jul-02 Release date: 20-Jan-04

Protein chains

P89116  (CASP1_SPOFR) -  Caspase-1

Seq: 299 a.a.

Struc: 247 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: apoptosis (2 terms)
• Biochemical function: hydrolase activity (4 terms)

DOI no: 10.1074/jbc.M312472200

J Biol Chem 279:7001-7008 (2004)

PubMed id: 14645217

Crystal structure of an invertebrate caspase.

C.M.Forsyth, D.Lemongello, D.J.LaCount, P.D.Friesen, A.J.Fisher.

ABSTRACT

Caspases play an essential role in the execution of apoptosis. These cysteine proteases are highly conserved among metazoans and are translated as inactive zymogens, which are activated by proteolytic cleavages to generate the large and small subunits and remove the N-terminal prodomain. The 2.3 A resolution crystal structure of active Sf-caspase-1, the principal effector caspase of the insect Spodoptera frugiperda, is presented here. The structure represents the first nonhuman caspase to be resolved. The structure of the cleaved and active protease was determined with the tetrapeptide inhibitor N-acetyl-Asp-Glu-Val-Asp-chloromethylketone covalently bonded to the active site cysteine. As expected, the overall fold of Sf-caspase-1 is exceedingly similar to that of the five active caspases from humans solved to date. The overall structure and active site arrangement of Sf-caspase-1 is most comparable with that of the human effector caspases, with which it shares highest sequence homology. The most prominent structural difference with Sf-caspase-1 is the position of the N-terminal region of the large subunit. Unlike the N terminus of human caspases, the N terminus of Sf-caspase-1 originates from the active site side where it interacts with active site loop L2 and then extends to the backside of the heterodimer. This unusual structural arrangement raises the possibility that the N-terminal prodomain plays a regulatory role during effector caspase activation or enzyme activity in insects.

Selected figure(s)

Figure 1.
FIG. 1. Sf-caspase-1 structure. Stereo ribbon drawing of the insect effector caspase determined at 2.3 Å resolution. Shown is one biologically active dimer of p19-p12 heterodimers. The p19 large subunits are colored blue and red on the outside. The p12 small subunits are colored cyan and pink and lie adjacent to the 2-fold, which is approximately perpendicular to the page. The secondary structural elements are labeled in pink on the left p19-p12 heterodimer ( -strands with numbers, -helices with capital letters) along with the termini. The position of the p19 N-terminal region, which forms a short -strand ( a), is seen interacting with the C terminus of the 2-fold-related p19 subunit. The two active sites are identified by the bound Ac-DEVD-cmk tetrapeptide inhibitor are shown in ball-and-stick. The inhibitor is covalently bound to the active site Cys178 located in the 4- 5 loop. The four loops that define the active site pocket are labeled L1-L4 (the loop designation is that found in Ref. 46). L2 consists of the loop between the C-terminal p19 and N-terminal p12 that is cleaved upon activation to form L2 and L2'. Figs. 1, 2, 3 were generated with BOBSCRIPT (59) and rendered with RASTER3D (60).

Figure 4.
FIG. 4. Detailed inhibitor-Sf-caspase-1 interactions. Shown is a flattened representation of the tetrapeptide inhibitor Ac-DEVD-cmk (thick gray bonds) and all of the caspase residues from the p19 large subunit (blue bonds) and p12 small subunit (teal-green bonds) that interact with bound inhibitor. The magenta dashed lines show potential hydrogen bonds between atoms with the numbers expressing the average distance (in Å) among the three active sites in the crystallographic asymmetric unit. Inhibitor atoms with short red lines represent hydrophobic interactions pointing toward the caspase residues also outlined with red lines. This figure was generated with LIGPLOT (61).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 7001-7008) copyright 2004.

Figures were selected by an automated process.