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.
Based on the crystal structure of the papain-E-64-c complex, 3-dimensional binding modes of a series of epoxysuccinyl amino acid derivatives to the papain active site have been constructed and the structure-inhibitory activity relationship has been analyzed using the accessible surface area and nonbonded energy parameters. The result indicates the importance of the hydrophobic interaction between the amino acid side chain of the inhibitor and the papain Val-157 residue for revealing the potent inhibitory activity.
Yamamoto
D
D
Osaka University of Pharmaceutical Sciences, Japan.
Matsumoto
K
K
Ohishi
H
H
Ishida
T
T
Inoue
M
M
Kitamura
K
K
Hanada
K
K
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000494:pharmacology*; D001665:Binding Sites; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010206:Papain / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013386:Succinates / Q000494:pharmacology; D014633:Valine
D000596:Amino Acids; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D011480:Protease Inhibitors; D013386:Succinates; D010206:Papain; D014633:Valine