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PDBsum entry 2oz2
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References listed in PDB file
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Key reference
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Title
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Vinyl sulfones as antiparasitic agents and a structural basis for drug design.
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Authors
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I.D.Kerr,
J.H.Lee,
C.J.Farady,
R.Marion,
M.Rickert,
M.Sajid,
K.C.Pandey,
C.R.Caffrey,
J.Legac,
E.Hansell,
J.H.Mckerrow,
C.S.Craik,
P.J.Rosenthal,
L.S.Brinen.
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Ref.
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J Biol Chem, 2009,
284,
25697-25703.
[DOI no: ]
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PubMed id
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Abstract
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Cysteine proteases of the papain superfamily are implicated in a number of
cellular processes and are important virulence factors in the pathogenesis of
parasitic disease. These enzymes have therefore emerged as promising targets for
antiparasitic drugs. We report the crystal structures of three major parasite
cysteine proteases, cruzain, falcipain-3, and the first reported structure of
rhodesain, in complex with a class of potent, small molecule, cysteine protease
inhibitors, the vinyl sulfones. These data, in conjunction with comparative
inhibition kinetics, provide insight into the molecular mechanisms that drive
cysteine protease inhibition by vinyl sulfones, the binding specificity of these
important proteases and the potential of vinyl sulfones as antiparasitic drugs.
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Figure 1.
The structures of cruzain, rhodesain, and falcipain-3. Ribbon
representation and superimposition of cruzain (pink), rhodesain
(aquamarine), and falcipain-3 (yellow) are shown. Insertions in
falcipain-3 are colored purple. All structure figures were
prepared in PyMOL (DeLano, 2002).
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Figure 3.
The active sites of cruzain (A), rhodesain (B), and
falcipain-3 (C).Ball and stick representation shows the
conserved catalytic triad and other important residues. The
figure is colored as in Fig. 1 with each inhibitor in gray.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
25697-25703)
copyright 2009.
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