Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1.

Johannes van den Boom, Franziska Trusch, Lukas Hoppstock, Christine Beuck, Peter Bayer (Corresponding Author)

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Article numbere0151431
Pages (from-to)1-13
Number of pages13
JournalPloS ONE
Volume11
Issue number3
DOIs
Publication statusPublished - 14 Mar 2016

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Myeloid-Lymphoid Leukemia Protein
asparaginase
Asparaginase
leukemia
Peptide Hydrolases
proteinases
helix-turn-helix motifs
Helix-Turn-Helix Motifs
Chemical activation
Proteolysis
circular dichroism spectroscopy
proteins
crystal structure
hydrolases
childhood
active sites
proteolysis
Nuclear magnetic resonance spectroscopy
Conformations
nuclear magnetic resonance spectroscopy

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Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1. / van den Boom, Johannes; Trusch, Franziska; Hoppstock, Lukas; Beuck, Christine; Bayer, Peter (Corresponding Author).

In: PloS ONE, Vol. 11, No. 3, e0151431, 14.03.2016, p. 1-13.

Research output: Contribution to journalArticle

van den Boom, Johannes ; Trusch, Franziska ; Hoppstock, Lukas ; Beuck, Christine ; Bayer, Peter. / Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1. In: PloS ONE. 2016 ; Vol. 11, No. 3. pp. 1-13.
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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.",
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