title: The SEP domain of p47 acts as a reversible competitive inhibitor of cathepsin L.
abstract: The solution structure of the human p47 SEP domain in a construct comprising residues G1-S2-p47(171-270) was determined by NMR spectroscopy. A structure-derived hypothesis about the domains' function was formulated and pursued in binding experiments with cysteine proteases. The SEP domain was found to be a reversible competitive inhibitor of cathepsin L with a Ki of 1.5 microM. The binding of G1-S2-p47(171-270) to cathepsin L was mapped by biochemical assays and the binding interface was investigated by NMR chemical shift perturbation experiments.
authors.affiliation: Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle Str. 10, D-13125 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Soukenik
authors.forename: Anne
authors.initials: A
authors.lastname: Diehl
authors.forename: Martina
authors.initials: M
authors.lastname: Leidert
authors.forename: Volker
authors.initials: V
authors.lastname: Sievert
authors.forename: Konrad
authors.initials: K
authors.lastname: Büssow
authors.forename: Dietmar
authors.initials: D
authors.lastname: Leitner
authors.forename: Dirk
authors.initials: D
authors.lastname: Labudde
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Ball
authors.forename: Annette
authors.initials: A
authors.lastname: Lechner
authors.forename: Dorit K
authors.initials: DK
authors.lastname: Nägler
authors.forename: Hartmut
authors.initials: H
authors.lastname: Oschkinat
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002401:Cathepsin B / Q000737:chemistry / Q000378:metabolism; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D017931:DNA Primers; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D015853:Cysteine Proteinase Inhibitors; D017931:DNA Primers; D010446:Peptide Fragments; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534130:CTSK protein, human; D056657:Cathepsin K