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

doi:10.1371/journal.pone.0151431

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)

Medical Sciences

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

4 Downloads (Pure)

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 language	English
Article number	e0151431
Pages (from-to)	1-13
Number of pages	13
Journal	PloS ONE
Volume	11
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0151431
Publication status	Published - 14 Mar 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pone.0151431Licence: CC BY

Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1
Copyright: © 2016 van den Boom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
Final published version, 1.97 MBLicence: CC BY

Cite this

@article{fe2a50c4a0f6425f9735ef5ff0472bb5,

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. ",

author = "{van den Boom}, Johannes and Franziska Trusch and Lukas Hoppstock and Christine Beuck and Peter Bayer",

note = "Acknowledgments We acknowledge the Fonds of Chemical Industry for funding JvdB by their Chemiefonds grant and the DFG for funding PB and CB (CRC 1093). Additional gratitude goes to Shirley Knauer for providing Taspase1 expression clones. Funding: The authors acknowledge the Fonds of Chemical Industry for funding JvdB by their Chemiefonds grant and the DFG for funding PB and CB (CRC 1093).",

year = "2016",

month = mar,

day = "14",

doi = "10.1371/journal.pone.0151431",

language = "English",

volume = "11",

pages = "1--13",

journal = "PloS ONE",

issn = "1932-6203",

publisher = "PUBLIC LIBRARY SCIENCE",

number = "3",

}

TY - JOUR

T1 - Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1.

AU - van den Boom, Johannes

AU - Trusch, Franziska

AU - Hoppstock, Lukas

AU - Beuck, Christine

AU - Bayer, Peter

N1 - Acknowledgments We acknowledge the Fonds of Chemical Industry for funding JvdB by their Chemiefonds grant and the DFG for funding PB and CB (CRC 1093). Additional gratitude goes to Shirley Knauer for providing Taspase1 expression clones. Funding: The authors acknowledge the Fonds of Chemical Industry for funding JvdB by their Chemiefonds grant and the DFG for funding PB and CB (CRC 1093).

PY - 2016/3/14

Y1 - 2016/3/14

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0151431

DO - 10.1371/journal.pone.0151431

M3 - Article

VL - 11

SP - 1

EP - 13

JO - PloS ONE

JF - PloS ONE

SN - 1932-6203

IS - 3

M1 - e0151431

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this