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PDBsum entry 1k3b
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Contents |
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119 a.a.
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164 a.a.
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69 a.a.
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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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Structure of human dipeptidyl peptidase i (cathepsin c): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases.
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Authors
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D.Turk,
V.Janjić,
I.Stern,
M.Podobnik,
D.Lamba,
S.W.Dahl,
C.Lauritzen,
J.Pedersen,
V.Turk,
B.Turk.
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Ref.
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Embo J, 2001,
20,
6570-6582.
[DOI no: ]
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PubMed id
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Abstract
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Dipeptidyl peptidase I (DPPI) or cathepsin C is the physiological activator of
groups of serine proteases from immune and inflammatory cells vital for defense
of an organism. The structure presented shows how an additional domain
transforms the framework of a papain-like endopeptidase into a robust oligomeric
protease-processing enzyme. The tetrahedral arrangement of the active sites
exposed to solvent allows approach of proteins in their native state; the
massive body of the exclusion domain fastened within the tetrahedral framework
excludes approach of a polypeptide chain apart from its termini; and the
carboxylic group of Asp1 positions the N-terminal amino group of the substrate.
Based on a structural comparison and interactions within the active site cleft,
it is suggested that the exclusion domain originates from a metallo-protease
inhibitor. The location of missense mutations, characterized in people suffering
from Haim-Munk and Papillon-Lefevre syndromes, suggests how they disrupt the
fold and function of the enzyme.
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Figure 3.
Figure 3 Active site cleft of DPPI with a bound model of the
N-terminal sequence ERIIGG from the biological substrate,
granzyme A. (A) Stereo view: covalent bonds of papain-like
domains and the exclusion domain are shown in the colors used in
Figure 1C. Covalent bonds of the substrate model are shown as
yellow sticks. Corresponding carbon atoms are shown as balls
using the covalent bond color scheme. The chloride ion is shown
as a large green sphere. Oxygen, nitrogen and sulfur atoms are
shown as red, blue and yellow spheres, respectively. The
residues relevant for substrate binding are marked and hydrogen
bonds are shown as white broken lines. The molecular surface was
generated with GRASP (Nicholls et al., 1991); the figure was
prepared in MAIN (Turk, 1992) and rendered with RENDER (Merritt
and Bacon, 1997). (B) Schematic presentation. The color codes
are the same as in (A).
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Figure 4.
Figure 4 Features of papain-like exopeptidases. A view towards
the active site clefts of superimposed papain-like proteases.
The underlying molecular surface of cathepsin L, shown in white,
is used to demonstrate an endopeptidase active site cleft, which
is blocked by features of the exopeptidase structures. The
surface of the catalytic cysteine is colored in yellow. Chain
traces of cathepsins B, X and H are shown in green, cyan and
purple, respectively. Chain traces of papain-like domains of
DPPI are shown in dark blue, whereas for the chain trace of the
exclusion domain the color code is the same as in Figure 1. The
bleomycin hydrolase chain trace is not shown for reasons of
clarity, although its C-terminal residues superimpose almost
perfectly with the C-terminal residues of the cathepsin H
mini-chain (purple).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
Embo J
(2001,
20,
6570-6582)
copyright 2001.
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