title: Defining the regulatory and inhibitory elements within the prodomain of CsCF-6, a cathepsin F cysteine protease of Clonorchis sinensis.
abstract: CsCF-6 is a member of the multigene family of cathepsin F cysteine proteases of Clonorchis sinensis. Similar to other papain family proteases, CsCF-6 is synthesized as a proenzyme and is converted to the mature form by autocatalytic removal of the prodomain. Here, we analyzed the regulatory and inhibitory elements within the CsCF-6 prodomain to understand the regulatory mechanism of CsCF-6 by its prodomain. The CsCF-6 prodomain played an essential role in the folding of CsCF-6. Particularly, the ERFNAQ motif within the prodomain was essential, and the minimum segment required for this event was the C-terminal part of the prodomain, including Asn(58) and downstream residues. The CsCF-6 prodomain effectively inhibited CsCF-6, in which the ERFNAQ motif played a critical role in the inhibition, but the GTFD motif was also required for complete inhibition of CsCF-6. The CsCF-6 prodomain showed broad inhibitory activity against several cysteine proteases. These results suggest that the CsCF-6 prodomain plays bi-functional roles in correct folding and inhibition of its cognate enzyme.
authors.affiliation: Department of Parasitology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Kang
authors.forename: Hye-Lim
authors.initials: HL
authors.lastname: Ju
authors.forename: Woon-Mok
authors.initials: WM
authors.lastname: Sohn
authors.forename: Byoung-Kuk
authors.initials: BK
authors.lastname: Na
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003004:Clonorchis sinensis / Q000201:enzymology*; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism*; D015801:Helminth Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017384:Sequence Deletion
chemical_list: D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D015801:Helminth Proteins; D002403:Cathepsins; C530512:CsCF-6 protein, Clonorchis sinensis
keywords: Cathepsin F; Clonorchis sinensis; Folding; Inhibition; Prodomain