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PDBsum entry 2c0y
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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 crystal structure of a cys25 -≫ ala mutant of human procathepsin s elucidates enzyme-Prosequence interactions.
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Authors
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G.Kaulmann,
G.J.Palm,
K.Schilling,
R.Hilgenfeld,
B.Wiederanders.
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Ref.
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Protein Sci, 2006,
15,
2619-2629.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of the active-site mutant Cys25 --> Ala of glycosylated
human procathepsin S is reported. It was determined by molecular replacement and
refined to 2.1 Angstrom resolution, with an R-factor of 0.198. The overall
structure is very similar to other cathepsin L-like zymogens of the C1A clan.
The peptidase unit comprises two globular domains, and a small third domain is
formed by the N-terminal part of the prosequence. It is anchored to the
prosegment binding loop of the enzyme. Prosegment residues beyond the prodomain
dock to the substrate binding cleft in a nonproductive orientation. Structural
comparison with published data for mature cathepsin S revealed that procathepsin
S residues Phe146, Phe70, and Phe211 adopt different orientations. Being part of
the S1' and S2 pockets, they may contribute to the selectivity of ligand
binding. Regarding the prosequence, length, orientation and anchoring of helix
alpha3p differ from related zymogens, thereby possibly contributing to the
specificity of propeptide-enzyme interaction in the papain family. The
discussion focuses on the functional importance of the most conserved residues
in the prosequence for structural integrity, inhibition and folding assistance,
considering scanning mutagenesis data published for procathepsin S and for its
isolated propeptide.
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Figure 5.
Figure 5. Interaction of the prosegment (cathepsin S, dark gray; cathepsin K, light gray; color code for numbering and chain) with the
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Figure 7.
Figure 7. C--H###p interactions between prosequence and active-site cleft
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The above figures are
reprinted
by permission from the Protein Society:
Protein Sci
(2006,
15,
2619-2629)
copyright 2006.
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Secondary reference #1
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Title
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Crystal structure of human cathepsin s.
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Authors
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M.E.Mcgrath,
J.T.Palmer,
D.Brömme,
J.R.Somoza.
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Ref.
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Protein Sci, 1998,
7,
1294-1302.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Structure of a cys25-->Ser mutant of human cathepsin s.
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Authors
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J.P.Turkenburg,
M.B.Lamers,
A.M.Brzozowski,
L.M.Wright,
R.E.Hubbard,
S.L.Sturt,
D.H.Williams.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2002,
58,
451-455.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2 Superposition of the active-site residues of mutant
cathepsin S (in red) and cathepsin K (in yellow). The
hydrogen-bonding network for the mutant enzyme is shown. The
catalytic triad (with the Ser25 mutation) is shown on the right,
with three water molecules in the centre and Gln19 and Trp186 to
the left. Hydrogen bonds are shown as dashed lines. The observed
network may provide a mechanism for correct catalytic residue
side-chain orientation prior to substrate hydrolysis. Also shown
is the final maximum-likelihood-weighted electron-density map
(2F[o] - F[c]), contoured at 1  above
the mean. This figure shows convincingly that the constellation
of the active-site residues is essentially unchanged in the
mutant.
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The above figure is
reproduced from the cited reference
with permission from the IUCr
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Secondary reference #3
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Title
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Specificity determinants of human cathepsin s revealed by crystal structures of complexes.
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Authors
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T.A.Pauly,
T.Sulea,
M.Ammirati,
J.Sivaraman,
D.E.Danley,
M.C.Griffor,
A.V.Kamath,
I.K.Wang,
E.R.Laird,
A.P.Seddon,
R.Ménard,
M.Cygler,
V.L.Rath.
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Ref.
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Biochemistry, 2003,
42,
3203-3213.
[DOI no: ]
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PubMed id
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