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PDBsum entry 1pe6
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Hydrolase (sulfhydryl proteinase)
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PDB id
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1pe6
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References listed in PDB file
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Key reference
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Title
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Refined X-Ray structure of papain.E-64-C complex at 2.1-A resolution.
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Authors
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D.Yamamoto,
K.Matsumoto,
H.Ohishi,
T.Ishida,
M.Inoue,
K.Kitamura,
H.Mizuno.
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Ref.
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J Biol Chem, 1991,
266,
14771-14777.
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PubMed id
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Abstract
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E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to
papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A
resolution were used to determine the three-dimensional structure of this
complex and refined it to R = 0.159. 0.159. In the complex structure, the
configurational conversion from S to R took place on the epoxy carbon of E-64-c,
implying that the nucleophilic attack of the Cys-25 thiol group occurs at the
opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of
E-64-c were strongly fixed to papain S subsites by specific interactions,
including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of
E-64-c formed an electrostatic interaction with the protonated His-159 imidazole
ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this
residue in the hydrolytic charge-relay system. No significant distortion caused
by the binding of E-64-c was shown in the secondary structure of papain. It is
important to note that inhibitor and substrate have opposite binding modes for
the peptide groups. The possible relationship between the binding mode and
inhibitory activity is discussed on the basis of the crystal structure of this
complex.
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Secondary reference #1
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Title
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Mode of binding of e-64-C, A potent thiol protease inhibitor, To papain as determined by X-Ray crystal analysis of the complex.
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Authors
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K.Matsumoto,
D.Yamamoto,
H.Ohishi,
K.Tomoo,
T.Ishida,
M.Inoue,
T.Sadatome,
K.Kitamura,
H.Mizuno.
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Ref.
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FEBS Lett, 1989,
245,
177-180.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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The importance of val-157 hydrophobic interaction for papain inhibitory activity of an epoxysuccinyl amino acid derivative. A structure-Activity relationship based on the crystal structure of the papain-E-64-C complex.
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Authors
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D.Yamamoto,
K.Matsumoto,
H.Ohishi,
T.Ishida,
M.Inoue,
K.Kitamura,
K.Hanada.
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Ref.
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FEBS Lett, 1990,
263,
134-136.
[DOI no: ]
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PubMed id
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