Milton T. Stubbs
Prof. Milton T. Stubbs
Prof. Stubbs (at top of the picture) with his research group
Institute for Biochemistry and Biotechnology/Physical Biotechnology
Kurt-Mothes-Straße 3
06120 Halle (Saale)
phone: +49 (0) 345-55 24901
milton.stubbs@biochemtech.uni-halle.de
Aminoglycoside antibiotic synthesis: Identification of protein assemblies for structural studies
The aminoglycosides (AGAs) kanamycin and tobramycin, which exert their antibiotic effects by binding to a deep groove in the aminoacyl decoding site of 16S ribosomal RNA, belong to a broader class of 2-deoxystreptamine (2-DOS) based compounds that include streptomycin and neomycin. Genetic analyses of AGA-producing organisms have allowed identification of gene clusters responsible for AGA biosynthesis and deduction of biosynthetic pathways. In collaboration with PD Dr. Udo F. Wehmeier of the Bergische Universität Wuppertal, we have initiated structural studies of AGA-biosynthesis enzymes, including the novel tobramycin O-carbamoyltransferase TobZ.
In this project, our goal is to establish methods to detect and analyse complexes of AGA-biosynthetic enzymes, with a view to structural analysis. In particular, we intend to apply the highly stable protein:peptide-ligand FimGt:DsF complex derived from the E. coli type 1 pilus-assembly machinery that has been adapted recently for tagged complex purification. Once established, the methodology is applicable to a wide range of existing and future collaborative projects within the Halle biosciences.