Physico-chemical and structural characterization of a new pharmaceutical target: the human Indoleamine-2,3-dioxygenase 2


Vall Brossa, Berta


L-Tryptophan (L-Trp) is an essential but also the least abundant amino acid. In the nature, it can be metabolized through different pathways. A small amount of our dietary L-Trp is degraded to synthesize proteins in the body. About 5% is used to synthesize serotonin and melatonin through the serotonin pathway, but the vast majority of it, ~95%, is metabolized through the kynurenine pathway (KP). The first and rate-limiting reaction of the KP, the conversion of L-Trp to N-formyl-kynurenine (NFK), is catalyzed by the enzymes indoleamine 2,3-dioxygenase (hIDO1, hIDO2). The KP produces many biologically active metabolites. Its final product, nicotinamide adenine dinucleotide (NAD+), plays a critical role in a wide range of cellular reactions. Unfortunately, the central role of this pathway can also be disastrous. The resulting shortage of L-Trp as well as generated kynurenine metabolites affect the activity of the immune and central nervous system. In the context detailed previously, the objectives of this master thesis are divided into two main blocks. A first part that consists in the production, the purification and the physico-chemical characterization of WT hIDO2. The second block destined to the structural characterization of the protein using crystallography that will later help the design of innovative inhibitors for this therapeutic target.



Wouters, Johan
Mirgaux, Manon


IQS SE - Undergraduate Program in Chemistry