title: Mode of binding of E-64-c, a potent thiol protease inhibitor, to papain as determined by X-ray crystal analysis of the complex.
abstract: 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.
authors.affiliation: Osaka University of Pharmaceutical Sciences, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: D
authors.initials: D
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Ohishi
authors.forename: K
authors.initials: K
authors.lastname: Tomoo
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Sadatome
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: H
authors.initials: H
authors.lastname: Mizuno
mesh_terms: 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
chemical_list: D011480:Protease Inhibitors; C032425:N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine; D010206:Papain; D007930:Leucine