title: The alpha1/2 helical backbone of the prodomains defines the intrinsic inhibitory specificity in the cathepsin L-like cysteine protease subfamily.
abstract: 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.
authors.affiliation: Fakultät für Chemie und Pharmazie, Universität Tübingen, Morgenstelle 8, D-72076, Tübingen, Germany.
authors.forename: Y L
authors.initials: YL
authors.lastname: Guo
authors.forename: U
authors.initials: U
authors.lastname: Kurz
authors.forename: J E
authors.initials: JE
authors.lastname: Schultz
authors.forename: C C
authors.initials: CC
authors.lastname: Lim
authors.forename: B
authors.initials: B
authors.lastname: Wiederanders
authors.forename: K
authors.initials: K
authors.lastname: Schilling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D010450:Endopeptidases; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010247:Paramecium / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D020539:Sequence Analysis, Protein; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D011993:Recombinant Fusion Proteins; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S