Research Network for Metals in Medicine

 

 

Dr Nicholas Edward Dixon

Position: Senior Fellow, Research School of Chemistry, Australian National University

Affiliation: Research School of Chemistry, Australian National University

Postal Address:
Research School of Chemistry, (Building 35)
Science Road
Australian National University
Canberra
A.C.T. 0200
AUSTRALIA

Phone: +61 (02) 6125 4391
Email: dixon@rsc.anu.edu.au
Webpage: http://rsc.anu.edu.au/RSC/ChemResearch/Chemists/dixon.html


Research Profile

Dr Dixon's research career has centred on developing understanding of the structures and functions of enzymes and proteins. He has made seminal contributions to research on binuclear metallohydrolases. As a PhD student, he discovered jack bean urease to be the first example of a natural nickel metalloenzyme, and as a result of careful mechanistic studies, proposed that the nickel ions were close together annd that both participated in the reaction. This novel mechanism turned out subsequently to be essentially true for urease, and to extend in a general sense to other binuclear metallohydrolases. Recent structures determined with collaborators and mechanistic studies showed that both aminopeptidase P and the proofreading subunit of DNA polymerase III have similar mechanisms. As a postdoc at ANU, he developed new and general methods for preparation of metal complexes and used them to study mechanisms of reactions of coordinated ligands as models for metalloenzymes. With Arthur Kornberg at Stanford, he was a key player in reconstitution of initiation of chromosomal DNA replication with purified proteins. He identified a novel factor required for this (protein HU). Since appointment to ANU, he has continued work on the structures and mechanisms of DNA replication proteins. His group has overproduced and purified more than fifty replication and other proteins, and used crystallography and NMR (in collaboration) to solve many important structures. Most significantly, Dixon initiated an international collaborative effort aimed at determining structures of the major hexameric replicative helicase (DnaB) and its complexes with other proteins, and he has recently defined the structural basis for proofreading by the replicative polymerase during DNA replication. Over the past few years, he initiated an adventurous long-term project involving development of selection and library construction methods for the directed molecular evolution of new protein structures and functions, and development of new core technologies for structural and functional genomics. A new methods have been described for protein cyclization using inteins and for in vitro preparative protein synthesis and labelling.

Selected Publications

  1. Levina, A., Lay, P.A. & Dixon, N.E. (2000) Disproportionation and nuclease activity of bis[2-ethyl-2-hydroxybutanoato(2-)]oxochromate(V) in neutral aqueous solutions. Inorg. Chem., 39, 385-395.
  2. Williams, N.K., Prosselkov, P., Liepinsh, E., Line, I., Sharipo, A., Littler, D.R., Curmi, P.M.G., Otting, G. & Dixon, N.E. (2002). In vivo protein cyclization promoted by a circularly-permuted Synechocystis sp. PCC6803 DnaB mini-intein. J. Biol. Chem., 277, 7790-7798.
  3. Hamdan, S., Carr, P.D., Brown, S.E., Ollis, D.L & Dixon, N.E. (2002). Structural basis for proofreading during replication of the Escherichia coli chromosome. Structure, 10, 535-546.
  4. Hamdan, S., Bulloch, E.M., Thompson, P.R., Beck, J.L., Yang, J.Y., Crowther, J.A., Lilley, P.E., Carr, P.D., Ollis, D.L., Brown, S.E. & Dixon, N.E. (2002). Hydrolysis of the 5'-p-nitrophenyl ester of TMP by the proofreading exonuclease (e) subunit of Escherichia coli DNA polymerase III. Biochemistry, 41, 5266-5275.
  5. Pintacuda, G., Keniry, M.A., Huber, T., Park, A.Y., Dixon, N.E. & Otting, G. (2004) Fast structure-based assignment of 15N-HSQC spectra of paramagnetic proteins. J. Am. Chem. Soc. Web Release Date: 13-Feb-2004; DOI: 10.1021/ja039339m.

Facilities

Facilities for study of protein structure and function. Expression of proteins in bacteria, protein purification, characterization by mass spectrometry, high-field NMR, protein X-ray crystallography, SPR analysis by BIACORE.

International Linkages

National Center for Biotechnology (CNB), madrid, SPAIN
BioMedical Center, Uppsala University, SWEDEN
Department of Medical Biochemistry and Biophysics, karolinska Institutet, Stockholm, SWEDEN