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PDBsum entry 1pci
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Thiol protease
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PDB id
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1pci
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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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The prosequence of procaricain forms an alpha-Helical domain that prevents access to the substrate-Binding cleft.
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Authors
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M.R.Groves,
M.A.Taylor,
M.Scott,
N.J.Cummings,
R.W.Pickersgill,
J.A.Jenkins.
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Ref.
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Structure, 1996,
4,
1193-1203.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Cysteine proteases are involved in a variety of cellular processes
including cartilage degradation in arthritis, the progression of Alzheimer's
disease and cancer invasion: these enzymes are therefore of immense biological
importance. Caricain is the most basic of the cysteine proteases found in the
latex of Carica papaya. It is a member of the papain superfamily and is
homologous to other plant and animal cysteine proteases. Caricain is naturally
expressed as an inactive zymogen called procaricain. The inactive form of the
protease contains an inhibitory proregion which consists of an additional 106
N-terminal amino acids; the proregion is removed upon activation. RESULTS: The
crystal structure of procaricain has been refined to 3.2 A resolution; the final
model consists of three non-crystallographically related molecules. The
proregion of caricain forms a separate globular domain which binds to the
C-terminal domain of mature caricain. The proregion also contains an extended
polypeptide chain which runs through the substrate-binding cleft, in the
opposite direction to that of the substrate, and connects to the N terminus of
the mature region. The mature region does not undergo any conformational change
on activation. CONCLUSIONS: We conclude that the rate-limiting step in the in
vitro activation of procaricain is the dissociation of the prodomain, which is
then followed by proteolytic cleavage of the extended polypeptide chain of the
proregion. The prodomain provides a stable scaffold which may facilitate the
folding of the C-terminal lobe of procaricain.
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Figure 7.
Figure 7. A diagram showing the proregion as it passes
through the substrate-binding cleft. The proregion is shown in
ball-and-stick representation and caricain is depicted as a
molecular surface representation; the most negative potentials
are shown in red, the most positive are in blue. The position of
Gly84p is indicated by the black arrow. The C-terminal domain of
caricain is towards the top of the picture and the position of
Asp158 is indicated. The surface is contoured at ± 12.5eV.
(Figure produced using GRASP [40].)
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1996,
4,
1193-1203)
copyright 1996.
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Secondary reference #1
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Title
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Determination of the structure of papaya protease omega
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Authors
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R.W.Pickersgill,
P.Rizkallah,
G.W.Harris,
P.W.Goodenough.
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Ref.
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acta crystallogr ,sect b, 1991,
47,
766.
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