Structural basis of inhibition of cysteine proteases by E-64 and its derivatives

• Published in: BIOPOLYM Vol. 51; no. 1; pp. 99 - 107
• Main Authors: Matsumoto, Keita, Mizoue, Kazutoshi, Kitamura, Kunihiro, Tse, Wai-Ching, Huber, Carol P., Ishida, Toshimasa
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 1999
• Subjects: actinidin; binding mode; Binding Sites; cathepsin B; cathepsin K; cathepsin L; Crystal structure; Crystallography, X-Ray; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - metabolism; cysteine protease; Cysteine Proteinase Inhibitors - chemical synthesis; Cysteine Proteinase Inhibitors - chemistry; Cysteine Proteinase Inhibitors - pharmacology; Drug Design; E-64; E-64 derivative; Epoxy Compounds; inhibitory mechanism; Leucine - analogs & derivatives; Leucine - chemical synthesis; Leucine - chemistry; Leucine - pharmacology; Models, Molecular; Molecular dynamics; Molecular structure; papain; Protein Conformation; Static Electricity; Structure-Activity Relationship; Succinic Acid

This paper focuses on the inhibitory mechanism of E‐64 and its derivatives (epoxysuccinyl‐based inhibitors) with some cysteine proteases, based on the binding modes observed in the x‐ray crystal structures of their enzyme–inhibitor complexes. E‐64 is a potent irreversible inhibitor against general c...