title: Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1.
abstract: Type 2 asparaginases, a subfamily of N-terminal nucleophile (Ntn) hydrolases, are activated by limited proteolysis. This activation yields a heterodimer and a loop region at the C-terminus of the α-subunit is released. Since this region is unresolved in all type 2 asparaginase crystal structures but is close to the active site residues, we explored this loop region in six members of the type 2 asparaginase family using homology modeling. As the loop model for the childhood cancer-relevant protease Taspase1 differed from the other members, Taspase1 activation as well as the conformation and dynamics of the 56 amino acids loop were investigated by CD and NMR spectroscopy. We propose a helix-turn-helix motif, which can be exploited as novel anticancer target to inhibit Taspase1 proteolytic activity.
authors.affiliation: Department of Structural and Medicinal Biochemistry, Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: van den Boom
authors.affiliation: Aberdeen Oomycetes Laboratory, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Franziska
authors.initials: F
authors.lastname: Trusch
authors.affiliation: Department of Structural and Medicinal Biochemistry, Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Hoppstock
authors.affiliation: Department of Structural and Medicinal Biochemistry, Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Beuck
authors.affiliation: Department of Structural and Medicinal Biochemistry, Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bayer
mesh_terms: D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism*; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship
chemical_list: D021122:Protein Subunits; D051788:Myeloid-Lymphoid Leukemia Protein; D010450:Endopeptidases; C480823:taspase1, human