title: Crystal structure of SCCA1 and insight about the interaction with JNK1.
abstract: Squamous cell carcinoma antigen 1 (SCCA1), which belongs to serine proteinase inhibitor (serpin) superfamily, inhibits papain-like cysteine proteinase. Recently, it has been reported that SCCA1 acts not only as a proteinase inhibitor but also as an inhibitor of UV-induced apoptosis via suppression of the activity of c-Jun NH(2)-terminal kinase (JNK1). The present study determined the crystal structure of SCCA1, suggesting that the reactive center loop (RCL) of SCCA1, a recognition site of proteinase, is very flexible and located away form the main-body of SCCA1. We show that the inhibitory effect of SCCA1 on the kinase activity of JNK1 is lost when the RCL was truncated. Furthermore, we found that a mutant protein created by replacing one amino acid in RCL maintain the suppressive activity to JNK1, whereas the inhibitory effect to proteinase is obviously decreased.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ku, Hiroshima 734-8551, Japan.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Matoba
authors.forename: Takanori
authors.initials: T
authors.lastname: Kumagai
authors.forename: Chika
authors.initials: C
authors.lastname: Katagiri
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hibino
authors.forename: Masanori
authors.initials: M
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation; D017433:Protein Structure, Secondary; D015843:Serpins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D048055:Mitogen-Activated Protein Kinase 8