PDBsum entry 1f0c

Viral protein

PDB id: 1f0c

Contents

Protein chains

297 a.a. *

36 a.a. *

Ligands

DTT

Waters ×167

* Residue conservation analysis

PDB id:

1f0c

Name:

Viral protein

Title:

Structure of the viral serpin crma

Structure:

Ice inhibitor. Chain: a. Fragment: residues 1-305. Synonym: cytokine response modifier protein, crma. Engineered: yes. Ice inhibitor. Chain: b. Fragment: residues 306-341. Synonym: cytokine response modifier protein, crma.

Source:

Cowpox virus. Organism_taxid: 10243. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.26Å R-factor: 0.228 R-free: 0.272

Authors:

M.Renatus,Q.Zhou,H.R.Stennicke,S.J.Snipas,D.Turk,L.A.Bankston, R.C.Liddington,G.S.Salvesen

Key ref:

M.Renatus et al. (2000). Crystal structure of the apoptotic suppressor CrmA in its cleaved form. Structure, 8, 789-797. PubMed id: 10903953 DOI: 10.1016/S0969-2126(00)00165-9

Date:

15-May-00 Release date: 06-Sep-00

Protein chain

P07385  (SPI2_CWPXB) -  Serine proteinase inhibitor 2 from Cowpox virus (strain Brighton Red)

Seq: 341 a.a.

Struc: 297 a.a.

Protein chain

P07385  (SPI2_CWPXB) -  Serine proteinase inhibitor 2 from Cowpox virus (strain Brighton Red)

Seq: 341 a.a.

Struc: 36 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1016/S0969-2126(00)00165-9

Structure 8:789-797 (2000)

PubMed id: 10903953

Crystal structure of the apoptotic suppressor CrmA in its cleaved form.

M.Renatus, Q.Zhou, H.R.Stennicke, S.J.Snipas, D.Turk, L.A.Bankston, R.C.Liddington, G.S.Salvesen.

ABSTRACT

BACKGROUND: Cowpox virus expresses the serpin CrmA (cytokine response modifier A) in order to avoid inflammatory and apoptotic responses of infected host cells. The targets of CrmA are members of the caspase family of proteases that either initiate the extrinsic pathway of apoptosis (caspases 8 and 10) or trigger activation of the pro-inflammatory cytokines interleukin-1beta and interleukin-18 (caspase 1). RESULTS: We have determined the structure of a cleaved form of CrmA to 2.26 A resolution. CrmA has the typical fold of a cleaved serpin, even though it lacks the N-terminal half of the A helix, the entire D helix, and a portion of the E helix that are present in all other known serpins. The reactive-site loop of CrmA was mutated to contain the optimal substrate recognition sequence for caspase 3; however, the mutation only marginally increased the ability of CrmA to inhibit caspase 3. Superposition of the reactive-site loop of alpha1-proteinase inhibitor on the cleaved CrmA structure provides a model for virgin CrmA that can be docked to caspase 1, but not to caspase 3. CONCLUSIONS: CrmA exemplifies viral economy, selective pressure having resulted in a 'minimal' serpin that lacks the regions not needed for structural integrity or inhibitory activity. The docking model provides an explanation for the selectivity of CrmA. Our demonstration that engineering optimal substrate recognition sequences into the CrmA reactive-site loop fails to generate a good caspase 3 inhibitor is consistent with the docking model.

Selected figure(s)

Figure 4.
Figure 4. Stereoview of the electron density. Parts of the central b sheet A (strands 3A, 4A, 5A and 6A, right to left, and turn s5As4A) are superimposed with the final 2F[o]-F[c] electron-density map contoured at 0.8s. The atoms are colored by type: blue, carbon; cyan, nitrogen; and red, oxygen. The figure was made with the program BobScript [49].

The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 789-797) copyright 2000.

Figure was selected by an automated process.