On the mechanism of promiscuous ligand-binding by multidrug resistance regulator LmrR and structural investigations of lytic transglycosylase MltF
PhD ceremony: Mr. P.K. Madoori, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: On the mechanism of promiscuous ligand-binding by multidrug resistance regulator LmrR and structural investigations of lytic transglycosylase MltF
Promotor(s): prof. B.W. Dijkstra
Faculty: Mathematics and Natural Scienes
LmrR (Lactococcal multidrug resistance Regulator) is a protein required by Lactococcus lactis to survive in the presence of toxic compounds. In response to chemically diverse compounds like ethidium and daunomycin, LmrR enhances the production of the major multidrug transporter LmrCD, which excretes the toxic compounds, thus preventing them to reach their cellular targets.
Crystal structures of LmrR in a drug-free state and with several bound drugs, as presented in this thesis, reveal the key structural determinants of its multidrug specificity. The LmrR structure contains a typical β-winged helix-turn-helix domain with an additional C-terminal helix involved in dimerization. Its dimeric organization is highly unusual with a hydrophobic pore at the dimer centre harbouring the multidrug-binding site. Planar lipophilic drugs bind in a similar manner with their aromatic rings sandwiched in between the indole groups of two dimer-related tryptophan residues. The use of a single site for binding different ligands, instead of a large binding site with partially overlapping subsites, and the dominating role of the dyad-related tryptophan residues in drug recognition and binding, distinguish LmrR from other well-characterized multidrug related transcriptional regulators.
Last modified: | 13 March 2020 01.00 a.m. |
More news
-
23 September 2024
Remove the ecologist from the ivory tower
It is clear as day that the Netherlands is facing great challenges in the area of nature conservation and biodiversity. According to ecologist Christ Smit, it is therefore high time that the scientist steps out of their ivory tower and joins the...
-
20 September 2024
European Green Deal: a double-edged sword for global emissions
The European Green Deal will bring the emission of greenhouse gases in the European Union down, but at the same time causes more than a twofold increase in emissions outside its borders.
-
05 September 2024
ERC Starting Grants for two UG researchers
Two UG researches, both working at the Faculty of Science and Engineering, have been awarded an ERC Starting Grant: Jingxiu Xie and Gosia Wlodarczyk-Biegun. The European Research Council's (ERC) Starting Grants consist of €1.5 million each, for a...