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.
Three researchers of the Faculty of Science and Engineering have been awarded an ENW-XS grant by the Dutch Research Council (Nederlandse Organisatie voor Wetenschappelijke Onderzoek, NWO): Prof. A.I. Guskov the Groningen Biomolecular Sciences and...
Bayu Jayawardhana has been appointed scientific director of DISC, the interuniversity research institute and graduate school that unites all university groups in the Netherlands that are active in systems and control theory and engineering. The...
Researchers Clemens Mayer and Danny Incarnato of the University of Groningen have been awarded an ERC Consolidator Grant.
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