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Structure-function study of a Ca2+-independent metacaspase involved in lateral root emergence

Stael, Simon (författare)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylära vetenskaper,Department of Molecular Sciences,Ghent University
Sabljić, Igor (författare)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylära vetenskaper,Department of Molecular Sciences
Audenaert, Dominique (författare)
VIB, Ghent, Belgium; Centre for Bioassay Development and Screening, Ghent University, Ghent, Belgium
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Andersson, Thilde (författare)
Umeå universitet,Kemiska institutionen
Tsiatsiani, Liana (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
Kumpf, Robert P. (författare)
Vidal-Albalat, Andreu (författare)
Umeå universitet,Kemiska institutionen
Lindgren, Cecilia (författare)
Umeå universitet,Kemiska institutionen
Vercammen, Dominique (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
Jacques, Silke (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
Nguyen, Long (författare)
VIB, Ghent, Belgium; Centre for Bioassay Development and Screening, Ghent University, Ghent, Belgium
Njo, Maria (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
Fernández-Fernández, Álvaro D (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
Beunens, Tine (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
Timmerman, Evy (författare)
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Center for Medical Biotechnology, VIB, Ghent, Belgium
Gevaert, Kris (författare)
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Center for Medical Biotechnology, VIB, Ghent, Belgium
Van Montagu, Marc (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
Ståhlberg, Jerry (författare)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylära vetenskaper,Department of Molecular Sciences
Bozhkov, Peter (författare)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylära vetenskaper,Department of Molecular Sciences
Linusson, Anna, 1970- (författare)
Umeå universitet,Kemiska institutionen
Beeckman, Tom (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
Van Breusegem, Frank (författare)
Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium; Center for Plant Systems Biology, VIB, Ghent, Belgium
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 (creator_code:org_t)
 
Proceedings of the National Academy of Sciences (PNAS), 2023
2023
Engelska.
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://pub.epsilon.... (primary) (Raw object) (free)
https://urn.kb.se/re...
https://doi.org/10.1...
https://res.slu.se/i...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Metacaspases are part of an evolutionarily broad family of multifunctional cysteine proteases, involved in disease and normal development. As the structure-function relationship of metacaspases remains poorly understood, we solved the X-ray crystal structure of an Arabidopsis thaliana type II metacaspase (AtMCA-IIf) belonging to a particular subgroup not requiring calcium ions for activation. To study metacaspase activity in plants, we developed an in vitro chemical screen to identify small molecule metacaspase inhibitors and found several hits with a minimal thioxodihydropyrimidine-dione structure, of which some are specific AtMCA-IIf inhibitors. We provide mechanistic insight into the basis of inhibition by the TDP-containing compounds through molecular docking onto the AtMCA-IIf crystal structure. Finally, a TDP-containing compound (TDP6) effectively hampered lateral root emergence in vivo, probably through inhibition of metacaspases specifically expressed in the endodermal cells overlying developing lateral root primordia. In the future, the small compound inhibitors and crystal structure of AtMCA-IIf can be used to study metacaspases in other species, such as important human pathogens, including those causing neglected diseases.

Ämnesord

LANTBRUKSVETENSKAPER  -- Bioteknologi med applikationer på växter och djur -- Växtbioteknologi (hsv//swe)
AGRICULTURAL SCIENCES  -- Agricultural Biotechnology -- Plant Biotechnology (hsv//eng)

Nyckelord

AtMCA-IIf crystal structure
cysteine protease
lateral root development
metacaspase
small chemical inhibitor

Publikations- och innehållstyp

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