Crystal structure and molecular conformation of E-64, a cysteine protease inhibitor.
In order to elucidate the conformational characteristics of cysteine protease inhibitors contributing to their inhibitory activities, the conformation of E-64 (N-[N-(L-3-trans-carboxyoxiran-2-carbonyl)-L-leucyl]-agmatine), a potent inhibitor of papain, was determined by X-ray crystal structure analysis. The molecules were packed in the crystal through electrostatic forces and hydrogen bonding between the oppositely charged terminal groups and between the amide groups. Two crystallographically independent E-64 molecules both took a flattened and slightly curved structure, which is similar to that of loxistatin, a related cysteine protease inhibitor. Based on the present results, a possible inhibitory mechanism of E-64 is proposed, with reference to the binding mode observed in the crystal structure of papain-substrate analogue complex.
Yamamoto
D
D
Matsumoto
K
K
Ishida
T
T
Inoue
M
M
Sumiya
S
S
Kitamura
K
K
D003460:Crystallization; D015853:Cysteine Proteinase Inhibitors / Q000032:analysis*; D007930:Leucine / Q000031:analogs & derivatives* / Q000032:analysis; D011487:Protein Conformation; D014961:X-Ray Diffraction
D015853:Cysteine Proteinase Inhibitors; D007930:Leucine; C024974:E 64