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PDBsum entry 4xui
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Hydrolase/hydrolase inhibitor
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PDB id
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4xui
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References listed in PDB file
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Key reference
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Title
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Synthesis and evaluation of oxyguanidine analogues of the cysteine protease inhibitor wrr-483 against cruzain.
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Authors
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B.D.Jones,
A.Tochowicz,
Y.Tang,
M.D.Cameron,
L.I.Mccall,
K.Hirata,
J.L.Siqueira-Neto,
S.L.Reed,
J.H.Mckerrow,
W.R.Roush.
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Ref.
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Acs Med Chem Lett, 2016,
7,
77-82.
[DOI no: ]
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PubMed id
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Abstract
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A series of oxyguanidine analogues of the cysteine protease inhibitor WRR-483
were synthesized and evaluated against cruzain, the major cysteine protease of
the protozoan parasite Trypanosoma cruzi. Kinetic analyses of these analogues
indicated that they have comparable potency to previously prepared vinyl sulfone
cruzain inhibitors. Co-crystal structures of the oxyguanidine analogues WRR-666
(4) and WRR-669 (7) bound to cruzain demonstrated different binding interactions
with the cysteine protease, depending on the aryl moiety of the P1' inhibitor
subunit. Specifically, these data demonstrate that WRR-669 is bound
noncovalently in the crystal structure. This represents a rare example of
noncovalent inhibition of a cysteine protease by a vinyl sulfone inhibitor.
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