Profiles

Pål Stenmark

Pål Stenmark

Docent

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Arbetar vid Institutionen för biokemi och biofysik
Telefon 08-16 37 29
E-post pal.stenmark@dbb.su.se
Besöksadress Svante Arrhenius väg 16
Rum A 467
Postadress Institutionen för biokemi och biofysik 106 91 Stockholm

Forskning

Structural and biophysical studies of Botulinum neurotoxins and novel Cancer targets in nucleotide metabolism

- The botulinum neurotoxins

The botulinum neurotoxins are the most toxic substances known; they are one million times more toxic than the cobra toxin. In spite of their extreme toxicity there has been a rapid expansion of the medical applications for the botulinum neurotoxins, with new applications constantly being discovered. This line of treatment is becoming the standard procedure for many conditions. The toxins are possible agents for bioterrorism and the development of countermeasures and vaccines are of high priority. We are studying the toxins using a wide variety of methods, including X-ray crystallography, to understand toxins basic mechanism and to improve their therapeutic properties. 

 

 

Structure of Botulinum neurotoxin type B bound to two receptors on the neuronal

 

- Structure based drug design

We also study enzymes involved in the nucleotide metabolism. One example is MTH1, this protein is important for clearing oxidative damage from the nucleotide pool. Many types of cancer cells have high levels of oxidative damage and depend on MTH1 for survival. We use X-ray crystallography to study the binding of MTH1 to natural substrates and potent inhibitors that we are developing in an interdisciplinary research collaboration. We use structural based drug design to refine these inhibitors into novel cancer drugs.

 

The crystal structure of human MTH1 in complex with a key inhibitor.

 

Group members

Jonathan Davies, Postdoc

Geoffrey Masuyer, Postdoc

Emma Rose Scaletti, Postdoc

Jana Skerlova, Postdoc

Linda Henriksson, PhD Student

Sara Kosenina, PhD Student

Markel Martinez, PhD Student

Daniel Rehling, PhD Student

 

Selected Publications

  • Dong M, Masuyer G, Stenmark P. (2019)
    Botulinum and Tetanus neurotoxins
    Annual Review of Biochemistry. 2019

  • Visnes T, Cázares-Körner A, Hao W, Wallner O, Masuyer G, Loseva O, Mortusewicz O, Wiita E, Sarno A, Manoilov A, Astorga-Wells J, Jemth AS, Pan L, Sanjiv K, Karsten S, Gokturk C, Grube M, Homan EJ, Hanna BMF, Paulin CBJ, Pham T, Rasti A, Berglund UW, von Nicolai C, Benitez-Buelga C, Koolmeister T, Ivanic D, Iliev P, Scobie M, Krokan HE, Baranczewski P, Artursson P, Altun M, Jensen AJ, Kalderén C, Ba X, Zubarev RA, Stenmark P, Boldogh I, Helleday T. (2018)
    Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
    Science. 2018 Nov 16;362(6416):834-839.

  • Zhang S, Masuyer G, Zhang J, Shen Y, Lundin D, Henriksson L, Miyashita S, Martínez-Carranza M, Dong M, Stenmark P. (2017)
    Identification and characterization of a novel botulinum neurotoxin
    Nature Communications. 2017 Aug 3;8:14130.

  • Masuyer G, Conrad J, Stenmark P. (2017)
    The structure of the tetanus toxin reveals pH-mediated domain dynamics.
    EMBO Reports. 2017 Aug;18(8):1306-1317. 

  • Carter M, Jemth AS, Hagenkort A, Page BD, Gustafsson R, Griese JJ, Gad H, Valerie NC, Desroses M, Boström J, Warpman Berglund U, Helleday T, Stenmark P(2015)
    Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2.
    Nature Communications. 2015 Aug 4;6:7871.

  • Gad H, Koolmeister T, Jemth A, Eshtad S, Jacques S, Ström C, Svensson L, Schultz N, Lundbäck T, Einarsdottir, Saleh A, Göktürk C, Baranczewski P, Svensson R, Berntsson R, Gustafsson R, Strömberg K, Sanjiv K, Jacques-Cordonnier M, Desroses M, Gustavsson A, Olofsson R, Johansson F, Homan E, Loseva O, Bräutigam L, Johansson L, Höglund A, Hagenkort A, Pham T, Altun M, Gaugaz F, Vikingsson S, Evers B, Henriksson M, Vallin K, Wallner O, Hammarström L, Wiita E, Almlöf E, Kaldéren C, Axelsson H, Puigvert J, Häggblad M, Jeppsson F, Martens U, Lundin C, Lundgren B, Granelli I, Jenmalm-Jensen A, Artursson P, Nilsson J, Stenmark P, Scobie M, Warpman-Berglund U, Helleday T. (2014)
    MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.
    Nature. 2014 Apr 10;508(7495):215-21.

  • Berntsson RP, Peng L, Dong M, Stenmark P(2013)
    Structure of dual receptor binding to botulinum neurotoxin B.
    Nature communications, 2013 Jun 28;4:2058

Funding Sources

Our research is supported by grants from the Swedish Research Council, the Wenner-Gren Foundations, the Carl Tryggers foundation, The Knut and Alice Wallenberg Foundation and the Swedish Cancer Society. 

Senast uppdaterad: 3 december 2018

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