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PDBsum entry 8pch
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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 porcine cathepsin h determined at 2.1 a resolution: location of the mini-Chain c-Terminal carboxyl group defines cathepsin h aminopeptidase function.
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Authors
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G.Guncar,
M.Podobnik,
J.Pungercar,
B.Strukelj,
V.Turk,
D.Turk.
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Ref.
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Structure, 1998,
6,
51-61.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Cathepsin H is a lysosomal cysteine protease, involved in
intracellular protein degradation. It is the only known mono-aminopeptidase in
the papain-like family and is reported to be involved in tumor metastasis. The
cathepsin H structure was determined in order to investigate the structural
basis for its aminopeptidase activity and thus to provide the basis for
structure-based design of synthetic inhibitors. RESULTS: The crystal structure
of native porcine cathepsin H was determined at 2.1 A resolution. The structure
has the typical papain-family fold. The so-called mini-chain, the octapeptide
EPQNCSAT, is attached via a disulfide bond to the body of the enzyme and bound
in a narrowed active-site cleft, in the substrate-binding direction. The
mini-chain fills the region that in related enzymes comprises the non-primed
substrate-binding sites from S2 backwards. CONCLUSIONS: The crystal structure of
cathepsin H reveals that the mini-chain has a definitive role in substrate
recognition and that carbohydrate residues attached to the body of the enzyme
are involved in positioning the mini-chain in the active-site cleft. Modeling of
a substrate into the active-site cleft suggests that the negatively charged
carboxyl group of the C terminus of the mini-chain acts as an anchor for the
positively charged N-terminal amino group of a substrate. The observed
displacements of the residues within the active-site cleft from their equivalent
positions in the papain-like endopeptidases suggest that they form the
structural basis for the positioning of both the mini-chain and the substrate,
resulting in exopeptidase activity.
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Figure 6.
Figure 6. Schematic representation of the mini-chain
binding. The mini-chain (bold lines) is covalently attached by
the Cys80P-Cys205 disulfide bridge to the R-domain. Three other
residues of the mini-chain form hydrogen bonds (dashed lines)
and stabilize the mini-chain position.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
51-61)
copyright 1998.
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