Johan Wouters

Structural biological chemistry and structure-based drug design

Gaining knowledge about the 3D structure of protein targets to accelerate new drug discovery for the treatment of cancer and infectious diseases

Prof. Johan Wouters PhD

UNamur, Department of chemistry, Unit of theoretical and structural physico-chemistry (UCPTS), Laboratory of structural biological chemistry (CBS) 

Member of Namur Research Institute for Life Sciences (NARILIS) & Namur Institute of Structured Matter (NISM)

Member of the Namur Medicine & Drug Innovation Center (NAMEDIC)

Research portal UNamur  |  ORCID  |  ResearchGate  |  LinkedIn

Expertise and research interests

Prof. Johan Wouters is leading a research group focusing on structural biological chemistry. His lab develops research projects falling within the field of medicinal chemistry and is an active member of the Namur Medicine & Drug Innovation Center (NAMEDIC). The research activities rely on a strong expertise in X-ray crystallography. Crystallography is a major tool for structure-based drug design, as it allows knowledge of the 3D structure of protein targets. In this context, researchers of the lab produce, purify, characterize and crystallize enzymes of pharmaceutical interest. Furthermore, X-ray crystallography is also used to determine the structure of small molecules with therapeutic potential. Researchers are focused on the preparation and physicochemical characterization of pharmaceutical cocrystals. The main research areas are cancer and infectious diseases.

Group members

Scientific collaborator: Dr. Laurence Leherte

Research logistician: Dr. Nikolay Tumanov

Postdoc: Dr. Mégane Van Gysel

PhD students: Xavier Garcia Llinas, Gilles Henon and Tanguy Scaillet

Research projects

  • ONGOING Structural study of Lactate Dehydrogenase, a target for the design of new anticancer agents. Postdoctoral research by Dr. Mégane Van Gysel.
  • ONGOING Design and synthesis of covalent disruptors to target the self-association of proteins. Ongoing PhD theses by Xavier Garcia Llinas, Gilles Henon and Tanguy Scaillet. Under co-supervision by Dr. Lionel Pochet and Prof. Johan Wouters.
  • Study of deracemizable pharmaceutical systems: towards an optimization and a rationalization of the screening step. Prof. Johan Wouters, UNamur (promoter) and Prof. Tom Leyssens, UCLouvain (co-promoter).
  • Preparation and physico-chemical characterization of (ionic) cocrystals of aryl hydantoins based on hydrogen, halogen, and chalcogen bonds. Postdoctoral research by Laurie Bodart (Oct 2021 - Mar 2023). Under co-supervision by Prof. Johan Wouters, UNamur (promoter) and Prof. Tom Leyssens, UCLouvain (co-promoter).

Selected publications

Pierson E, De Pol F, Fillet M, Wouters J. A morpheein equilibrium regulates catalysis in phosphoserine phosphatase SerB2 from Mycobacterium tuberculosis. Commun Biol. 2023 Oct 10;6(1):1024.

Mirgaux M, Leherte L, Wouters J. Human indoleamine-2,3-dioxygenase 2 cofactor lability and low substrate affinity explained by homology modeling, molecular dynamics and molecular docking. J Biomol Struct Dyn. 2023 Jun 10:1-14.

Mirgaux M, Scaillet T, Kozlova A, Tumanov N, Frederick R, Bodart L, Wouters J. Structural study of bioisosteric derivatives of 5-(1H-indol-3-yl)-benzotriazole and their ability to form chalcogen bonds. Acta Crystallogr E Crystallogr Commun. 2022 Mar 22;78(Pt 4):418-424.

Mirgaux M, Leherte L, Wouters J. Temporary Intermediates of L-Trp Along the Reaction Pathway of Human Indoleamine 2,3-Dioxygenase 1 and Identification of an Exo Site. Int J Tryptophan Res. 2021 Dec 15;14:11786469211052964.

Mambourg K, Tumanov N, Henon G, Lanners S, Garcia-Ladona J, Wouters J. Crystal structures of two alanyl-piperidine analogues. Acta Crystallogr E Crystallogr Commun. 2021 Oct 13;77(Pt 11):1095-1098.

Bodart L, Prinzo M, Derlet A, Tumanov N, Wouters J. Taking advantage of solvate formation to modulate drug–drug ratio in clofaziminium diclofenac salts. CrystEngComm. 2021. 23(1), pp. 185-201.

Mirgaux M, Leherte L, Wouters J. Influence of the presence of the heme cofactor on the JK-loop structure in indoleamine 2,3-dioxygenase 1. Acta Crystallogr D Struct Biol. 2020 Dec 1;76(Pt 12):1211-1221.

Bodart L, Derlet A, Buol X, Leyssens T, Tumanov N, Wouters J. Combining two antitubercular drugs, clofazimine and 4-aminosalicylic acid, in order to improve clofazimine aqueous solubility and 4-aminosalicylic acid thermal stability. J Pharm Sci. 2020 Dec;109(12):3645-3652.

Pierson E, Wouters J. Biochemical characterization of phosphoserine phosphatase SerB2 from Mycobacterium marinum. Biochem Biophys Res Commun. 2020 Oct 1;530(4):739-744.

Mambourg K, Bodart L, Tumanov N, Lanners S, Wouters J. Synthesis, crystal structure and conformational analysis of an unexpected [1,5]dithiocine product of aminopyridine and thiovanillin. Acta Crystallogr C Struct Chem. 2020 Mar 1;76(Pt3):205-211.

Pierson E, Haufroid M, Gosain TP, Chopra P, Singh R, Wouters J. Identification and Repurposing of Trisubstituted Harmine Derivatives as Novel Inhibitors of Mycobacterium tuberculosis Phosphoserine Phosphatase. Molecules. 2020 Jan 19;25(2):415.

Haufroid M, Mirgaux M, Leherte L, Wouters J. Crystal structures and snapshots along the reaction pathway of human phosphoserine phosphatase. Acta Crystallogr D Struct Biol. 2019 Jun 1;75(Pt 6):592-604.