NAmur Research Institute for LIfe Sciences
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).
- . PhD theses by Mégane Van Gysel on 20/02/2023.
- . PhD thesis by Manon Mirgaux on 16/11/2022.
- Biophysical and enzymological exploration of Mycobacterium tuberculosis phosphoserine phosphatase SerB2 self-assembly and regulation by L-serine. PhD thesis by Elise Pierson on 03/10/2022.
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Small molecules as therapeutic options in Parkinson’s disease: case of modulators of UCH-L1 and GLP-1 receptor. PhD thesis by Kalina Mambourg on 31/03/2022. Joint PhD at UNamur (Prof. Johan Wouters) and Abaxys Therapeutics.
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Structural and inhibition study of phosphoserine phosphatase (SerB2) from Mycobacterium tuberculosis. PhD thesis defended by Marie Haufroid on 25/03/2022.
- . PhD thesis defended by Andrea Carletta on 25/04/2019.
- Identification of chemosensitizing compounds inhibiting the resistance of taxol induced by TMEM45A protein on MDA-MB-231 cell line. PhD thesis defended by Sébastien Marx on 25/10/2019. Under co-supervision by Prof. Johan Wouters (promoter) and Prof. Carine Michiels (co-promoter).
- Structural and functional approach of the first enzyme of the serine synthesis pathway: PHGDH a potential target for cancer treatment. PhD thesis defended by Quentin Thémans on 18/10/2019.
- Structural and functional characterization of the transmembrane protein 45A (TMEM45A) in triple negative breast cancers. PhD thesis defended by Thomas Dal Maso on 04/10/2019. Under co-supervision by Prof. Johan Wouters (promoter) and Prof. Carine Michiels (co-promoter).
- Structural study of imines and phthalimides obtained by mechanosynthesis. PhD thesis defended by Jean Dubois on 24/11/2017.
- . PhD thesis defense by Grégoire Rondelet on 13/12/2016.
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.
