The α1/2 helical backbone of the prodomains defines the intrinsic inhibitory specificity in the cathepsin L‐like cysteine protease subfamily

FEBS Letters

Lim, Chin Chia¹  Wiederanders, B¹  Guo, Ying Lan²  Schultz, J.E²  Schilling, K¹  Kurz, Ursula² 

[1] Institut für Biochemie I, Klinikum der Friedrich-Schiller-Universität, Nonnenplan 2, D-07740 Jena, Germany;Fakultät für Chemie und Pharmazie, Universität Tübingen, Morgenstelle 8, D-72076 Tübingen, Germany

关键词: Papain family;    Propeptide;    Specificity;    Inhibition kinetics;    Paramecium;    NH-Mec;    7-amido-4-methylcoumarin;    CS;    human cathepsin S;    ppCS;    propeptide of human cathepsin S;    CL;    Paramecium cathepsin L;    ppCL;    propeptide of Paramecium cathepsin L;   

DOI  :  10.1016/S0014-5793(00)01281-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Proregions of papain-like cysteine proteases are potent and often highly selective inhibitors of their parental enzymes. The molecular basis of their selectivity is poorly understood. For two closely related members of the cathepsin L-like subfamily we established strong selectivity differences. The propeptide of cathepsin S was observed to inhibit cathepsin L with a K _i of 0.08 nM, yet cathepsin L propeptide inhibited cathepsin S only poorly. To identify the respective structural correlates we engineered chimeric propeptides and compared their inhibitory specificity with the wild-types. Specificity resided in the N-terminal part, strongly suggesting that the backbone of the prodomain was the underlying structure.

【 授权许可】

Unknown