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Schistosome sirtuins as drug targets

    Julien Lancelot

    Center for Infection & Immunity of Lille (CIIL), INSERM U1019 – CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, 1 rue Professeur Calmette, 59019 Lille Cedex, France

    ,
    Alejandro Cabezas-Cruz

    Center for Infection & Immunity of Lille (CIIL), INSERM U1019 – CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, 1 rue Professeur Calmette, 59019 Lille Cedex, France

    ,
    Stéphanie Caby

    Center for Infection & Immunity of Lille (CIIL), INSERM U1019 – CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, 1 rue Professeur Calmette, 59019 Lille Cedex, France

    ,
    Martin Marek

    Département de Biologie Structurale Intégrative, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UDS), CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France

    ,
    Johan Schultz

    Kancera AB, Karolinska Institutet Science Park, Banvaktsvägen 22, 171 48 Solna, Sweden

    ,
    Christophe Romier

    Département de Biologie Structurale Intégrative, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UDS), CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France

    ,
    Wolfgang Sippl

    Institute of Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany

    ,
    Manfred Jung

    Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstraße 25, 79104 Freiburg, Germany

    &
    Raymond J Pierce

    *Author for correspondence:

    E-mail Address: raymond.pierce@pasteur-lille.fr

    Center for Infection & Immunity of Lille (CIIL), INSERM U1019 – CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, 1 rue Professeur Calmette, 59019 Lille Cedex, France

    Published Online:https://doi.org/10.4155/fmc.15.24

    The sirtuins form a superfamily of evolutionarily conserved NAD+-dependent protein N-ϵ-acyl-lysine (AcK) deacylases with roles in a variety of key cellular processes. Sirtuins have a broadly conserved overall structure with a catalytic site formed by a hydrophobic channel between the NAD+-binding Rossmann fold domain and a smaller Zn2+-binding domain. Schistosomes express five members of the sirtuin family and generic sirtuin inhibitors induce apoptosis and death in schistosome larvae, the disruption of adult worm pairs, inhibition of egg laying and damage to the male and female worm reproductive systems. Sirtuins in schistosomes and other parasitic flatworms present structural differences from their human orthologues that should allow the development of selective inhibitors that can be developed as drug leads.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest.

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