Mode of binding of E-64-c, a potent thiol protease inhibitor, to papain as determined by X-ray crystal analysis of the complex.
The three-dimensional structure of the E-64-c-papain complex has been determined by X-ray crystal analysis at 2.5 A resolution (conventional R = 26.9%). The structure determined indicates that: (i) the C2 atom of the oxirane ring of E-64-c is covalently bound by the S gamma atom of Cys-25 of papain; (ii) this covalent bond formation results in a configurational conversion of the oxirane C2 atom from the S- to the R-form; and (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the specific interaction of the E-64-c molecule with papain.
Matsumoto
K
K
Osaka University of Pharmaceutical Sciences, Japan.
Yamamoto
D
D
Ohishi
H
H
Tomoo
K
K
Ishida
T
T
Inoue
M
M
Sadatome
T
T
Kitamura
K
K
Mizuno
H
H
D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D003196:Computer Graphics; D006860:Hydrogen Bonding; D007930:Leucine / Q000031:analogs & derivatives* / Q000378:metabolism; D010206:Papain / Q000378:metabolism*; D011480:Protease Inhibitors; D011487:Protein Conformation; D012984:Software; D014961:X-Ray Diffraction
D011480:Protease Inhibitors; C032425:N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine; D010206:Papain; D007930:Leucine