IMSS Seminar DATE: 2010-11-26 10:00 - PLACE: no data of english place field TITLE: The role of oligomerisation in enzyme function: Structure and evolution of an essential bacterial enzyme CONTACT: CHAVAS Leonard SPEAKER: Dr. Renwick C.J. Dobson LANGUAGE: English ABSTRACT: It is often unclear why enzymes are oligomeric. In some cases, oligomerisation provides a means of allosteric regulation. For the lysine biosynthetic enzyme dihydrodipicolinate synthase (DHDPS), dimerisation provides a pocket into which the allosteric inhibitor―lysine―can bind and inhibit catalysis. Whilst the dimer forms the allosteric cleft and contributes the active site, the reason for tetramerisation is less clear. The homotetrameric structure of DHDPS is essential for enzymatic activity, since dimeric mutants of E. coli DHDPS are much less active compared to the wild-type tetramer. We propose that by buttressing two dimers together, tetramerisation optimises protein dynamics for catalysis, particularly within the key catalytic triad motif. In general DHDPS enzymes appear to have evolved three conformations to solve the problem of excessive protein dynamics in the dimer: 1) tetramerisation as found in bacterial species (e.g. E. coli DHDPS), 2) tetramerisation as found in plant DHDPS enzymes, and 3) the Staphylococcus aureus-DHDPS dimer, which has stronger contacts across the dimer interface. I will present our ongoing work to uncover the mechanisms of catalysis and allostery. In addition, I will include our recent studies of the bacterial DHDPS enzymes from S. aureus, which is the first dimeric DHDPS enzyme characterised, and Clostridium botulinum, which shows a novel mechanism of regulation, whereby its substrate (pyruvate) promotes oligomerisation from less active monomers and dimers to an active tetramer. Dobson, R. C. J.1,2 1 Bio21 Molecular Science and Biotechnology Institute, Melbourne, Victoria, Australia. 2 Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Victoria, Australia Back