Skip to Main content Skip to Navigation
Master Thesis

Designing a drug against tuberculosis using crystallography: fragment-based screening targeting MtDS

Abstract : Tuberculosis is the deadliest infectious disease worldwide alongside HIV nowadays. It is in most cases a lung disease, caused by Mycobacterium tuberculosis. Actual treatments are long and have hepatotoxic side effects. Moreover, none is really effective against the drug-resistant strains, this is why there is an urgent need of new medicine. The Shikimate pathway is a way of producing aromatic amino-acids in bacteria that is absent in humans. MtDS, a key enzyme of the Shikimate pathway, is then a potential drug-target. In this project, the aim was to find a drug targeting MtDS by using a fragment-based screening analysed by X-ray crystallography. MtDS was expressed in E.coli and purified along with its homologous protein CgDS from Corynebacterium glutamicum. CgDS is a protein very similar to MtDS that could help its understanding and is easier to handle in a general way. The conditions for MtDS crystallisation were optimized in order to get diffracting crystals. These were soaked for 24h in compounds mixes of drug-like fragments from a library, and analysed by X-ray crystallography. Two datasets were successfully collected at a 3 Å resolution, with a CC1/2 superior to 30%. Further analyses need to be conducted in order to determine whether there are compounds bound to the protein or not.
Complete list of metadatas

https://dumas.ccsd.cnrs.fr/dumas-01360742
Contributor : Agrocampus Ouest <>
Submitted on : Tuesday, September 6, 2016 - 11:27:25 AM
Last modification on : Monday, July 6, 2020 - 3:38:21 PM
Long-term archiving on: : Wednesday, December 7, 2016 - 1:52:54 PM

Identifiers

  • HAL Id : dumas-01360742, version 1

Collections

Citation

Emanuelle Albat. Designing a drug against tuberculosis using crystallography: fragment-based screening targeting MtDS. Life Sciences [q-bio]. 2016. ⟨dumas-01360742⟩

Share

Metrics

Record views

119

Files downloads

98