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PDBsum entry 1f0c
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Viral protein
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PDB id
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1f0c
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the apoptotic suppressor crma in its cleaved form.
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Authors
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M.Renatus,
Q.Zhou,
H.R.Stennicke,
S.J.Snipas,
D.Turk,
L.A.Bankston,
R.C.Liddington,
G.S.Salvesen.
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Ref.
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Structure, 2000,
8,
789-797.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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].
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2000,
8,
789-797)
copyright 2000.
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