Staff profile

Dr Megan Maher

Senior Research Fellow, Lab Head

College of Science, Health and Engineering
School of Molecular Sciences
Department of Biochemistry and Genetics

Melbourne (Bundoora)

Area of study

Biochemistry and Molecular Biology

Brief profile


My research focuses on the structural biology of metals in biological systems, with particular emphasis on the technique of X-ray crystallography.

Research interests


- Please contact me to discuss a topic.

Recent publications

 Ash M.-R., Maher M. J., Guss J. M. and Jormakka M. The Structure of a N11A Mutant from the G-protein Domain of FeoB. Acta Crystallographica. 2011: F67: 1511-5. [Abstract]

Ash M.-R., Maher M. J., Guss J. M. and Jormakka M. A Suite of Switch I and Switch II Mutant Structures from the G-protein Domain of FeoB. Acta Crystallographica. 2011: D67: 973-80. [Abstract]

Ash, M., Maher, M., Guss, J., Jormakka, M. The Initiation of GTP Hydrolysis by the G-Domain of FeoB: Insights from a Transition-State Complex Structure. PloS One. 2011; 6:e23355. [Abstract]

Ash M.-R., Chong L. X., Maher M. J., Hinds M. G., Xiao Z. and Wedd A. G. Molecular Basis of the Cooperative Binding of Cu(I) and Cu(II) to the CopK protein from Cupriavidus metallidurans CH34 Biochemistry. 2011: 50: 9237-47. [Abstract]

Kilmartin J. R., Maher M. J., Krusong K., Noble C. J., Hanson G. R., Bernhardt P. V., Riley M. J. and Kappler U. Insights into Structure and Function of the Active Site of SoxAX Cytochromes. The Journal of Biological Chemistry. 2011: 28: 24872-81. [Abstract]

 Ash, M., Guilfoyle, A., Clarke, R., Guss, M., Maher, M., Jormakka, M. Potassium-activated GTPase reaction in the G protein coupled ferrous iron transporter B. The Journal of biological chemistry. 2010; 285:14594-602. [Abstract]

Guilfoyle, A., Maher, M., Rapp, M., Clarke, R., Harrop, S., Jormakka, M. Structural basis of GDP release and gating in G protein coupled Fe(2+) transport. The EMBO journal. 2009; 28:2677-85. [Abstract]

Maher M. J., Akimoto S., Iwata M., Nagata K., Hori Y., Yoshida M., Yokoyama S., Iwata S., Yokoyama K. Crystal Structure of the A(3)B(3) complex of V-ATPase from Thermus thermophilus. The EMBO Journal. 2009: 28: 3771-3779. [Abstract]

Research projects

Metals in Biology

Nearly 30% of all proteins require interaction with a metal ion for biological activity. The mechanisms by which cellular systems acquire essential transition row metals, such as Mn, Fe, Cu, and Zn, at concentrations necessary to support such processes until recently were poorly understood.  Originally, the interiors of cells were perceived as metal ‘soups’, containing significant concentrations of essential trace metals in ‘free’ forms readily available for insertion as cofactors into proteins and enzymes. This idea evolved from the observation that in vitro many metalloproteins bind metals with extremely high affinities. However, it is now recognized that within cells, there exist specific uptake, resistance, transport and metallo-regulatory systems, which protect organisms against transition metal stresses, and specifically incorporate metals into the proteins and enzymes that require them.

My research investigates the roles of metals in biology in two areas: (1) metals in electron-transfer processes; (2) cellular metal homeostasis – metal transport proteins, in particular.

Metals in electron-transfer processes

(Collaborator: Dr Ulrike Kappler, University of Queensland)

Sulfite is the product of a number of environmental and metabolic processes. It is reactive and must be converted to sulfate. This reaction is mediated by the sulfite oxidizing enzymes.  We are examining the sulfite oxidation pathway from the organism Sinorhizobium meliloti. For this bacterium, sulfite oxidation plays a role in energy production and metabolism.  Current projects aim to solve the structure of the sulfite oxidase enzyme from Sinorhizobium meliloti (SorT) and those of its likely redox partners (cytochrome c and pseudoazurin) in order to understand the molecular mechanism of sulfite oxidation by this bacterium.

Metal homeostasis – the structures of metal transport proteins

Metals such as manganese and iron are essential to all forms of life.  During bacterial infection, microbes acquire trace metals from the host.  The innate immune response from the host is to sequester these metals away from infecting bacteria in order to suppress pathogenesis.  We are investigating whether interference with bacterial metal acquisition can provide a novel target for antibiotic design.

 FeoB – ferrous iron uptake

(Collaborators A/Prof Mika Jormakka, Centenary Institute; A/Prof. Renae Ryan, University of Sydney; Prof. Iain Lamont, University of Otago).

FeoB is the major pathway for ferrous iron uptake for bacteria, which live in acidic or anaerobic environments. The protein has a unique topology, with an intracellular GTPase domain tethered directly to an integral membrane domain.  We are endeavouring to solve the structure of FeoB using X-ray crystallography, to understand how GTP hydrolysis is coupled to ferrous iron transport.

 PsaBCA – manganese uptake by Streptococcus pneumoniae.

(Collaborator: Dr Christopher McDevitt, University of Adelaide).

Manganese is essential for many bacterial species as it is required for enzymes, which respond to oxidative stress.  The ABC transporter PsaBCA from Streptococcus pneumoniae is a virulence factor for this organism and is essential for manganese uptake.  We are working towards the structure solution of this protein by X-ray crystallography with a view to using it as a scaffold for novel antibiotic design.