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POST-DOCTORAL RESEARCH FELLOW Elucidation of substrate recognition and reaction mechanism in the methyltransferases of cobalamin biosynthesis A BBSRC-funded postdoctoral post is available immediately, for 3 years, to elucidate the structures of methyltransferases both free and in complex with their tetrapyrrole substrates. The methyltransferases catalyse no fewer than six of the 30 enzyme-mediated steps in the biosynthesis of vitamin B12 (cobalamin) from 5-aminolevulinic acid. These methylations prevent reversible C-protonation and leads to the formation of particular tautomeric intermediates. The specific spatial and temporal addition of the eight methylations on the macrocycle reveals the importance of forming the correct double bond configurations essential for much of the chemistry that is required for corrin ring synthesis. The coupling of methylation and ring contraction is an exemplar. The post is mainly concerned with the crystallization and X-ray crystal structure determination of the enzymes and complexes and some of the enzymes have already been crystallized. There are also opportunities to be involved in the production of enzymes and tetrapyrrole intermediates, and thermodynamic and kinetic analyses. Crystallization of the oxygen-sensitive intermediates will make use of anaerobic crystallization facilities. A PhD in a relevant subject area and a strong research background in protein crystallography and protein chemistry are required. Application deadline 3 November 2006. The post is based at Queen Mary, University of London. Informal enquiries to: Prof Richard Pickersgill, tel: +44 (0)20 78826360, email: [EMAIL PROTECTED] or Prof. Martin Warren, tel: +44 (0)1227 824690, email:[EMAIL PROTECTED] ------------------------------------------------------------------------------ Richard W Pickersgill School of Biological and Chemical Sciences Queen Mary, University of London Mile End Road London E1 4NS T: 02078826360 F: 02089830973 E: [EMAIL PROTECTED] ------------------------------------------------------------------------------
