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PDBsum entry 1me3
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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 structures of reversible ketone-Based inhibitors of the cysteine protease cruzain.
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Authors
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L.Huang,
L.S.Brinen,
J.A.Ellman.
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Ref.
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Bioorg Med Chem Lett, 2003,
11,
21-29.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structures of two hydroxymethyl ketone inhibitors complexed to the
cysteine protease cruzain have been determined at 1.1 and 1.2 A resolution,
respectively. These high resolution crystal structures provide the first
structures of non-covalent inhibitors bound to cruzain. A series of compounds
were prepared and tested based upon the structures providing further insight
into the key binding interactions.
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Secondary reference #1
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Title
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A target within the target: probing cruzain'S p1' Site to define structural determinants for the chagas' Disease protease.
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Authors
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L.S.Brinen,
E.Hansell,
J.Cheng,
W.R.Roush,
J.H.Mckerrow,
R.J.Fletterick.
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Ref.
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Structure, 2000,
8,
831-840.
[DOI no: ]
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PubMed id
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Figure 6.
Figure 6. Surface representation of the cruzain active-site
region. Hydrophobic residues are indicated in green. (Note that
the sides of the S2 pocket are lined with hydrophobic patches.)
The surfaces of amino acids of interest (see text) are labeled
and color coded: Gln19 and His159, cyan; Asp158 and Ser139,
magenta; Cys25 and Met142, yellow. Inhibitor molecules are
displayed as sticks. (a) VSI, (b) VSII, (c) VSIII, (d) VSIV.
This figure was prepared with the program GRASP [44].
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The above figure is
reproduced from the cited reference
with permission from Cell Press
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Secondary reference #2
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Title
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The crystal structure of cruzain: a therapeutic target for chagas' Disease.
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Authors
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M.E.Mcgrath,
A.E.Eakin,
J.C.Engel,
J.H.Mckerrow,
C.S.Craik,
R.J.Fletterick.
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Ref.
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J Mol Biol, 1995,
247,
251-259.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. The alpha carbon trace
for cruzain (green) and papain (pink)
which have been optimally superim-
posed, is shown for the region of
the Cys153-Cys200 disulfide bond.
Neighboring insertions and del-
etions in the 2 proteins shift the
position of this conserved disulfide
bond. The side-chains for the cys-
teine residues are shown in yellow
and the catalytic triad is shown for
papain.
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Figure 3.
Figure 3. Equivalent view of the
cruzain (right) and papain (left) S2
substrate binding sites with Z-Phe-
Ala-FMK bound. The Z moiety has
been deleted to better show the
interactions made with the proteases
by Phe at P2 of the inhibitor. Atoms
of cruzain and papain are shown
with solvent accessible surfaces
while the inhibitor is shown as a solid
surface rendering in pink. There is a
60° rotation of the Phe side-chain in
cruzain relative to papain. The 5
residues which comprise S2 differ in
the 2 enzymes. Papain makes twice
as many van der Waals contacts with
Phe as cruzain does.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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