Professor Alice Vrielink
Molecular Sciences, School of
- Contact details
- School of Molecular Sciences
The University of Western Australia (M310)
35 Stirling Highway
CRAWLEY WA 6009
- +61 8 6488 3162
- +61 8 6488 7330
- Personal homepage
- Room 431, Bayliss Building, Perth campus
- BSc MSc Calg., PhD Lond.
- Professor Alice Vrielink obtained her Bachelor of Science in Chemistry and Masters of Science in Physical Chemistry at the University of Calgary in Canada. She then completed a PhD in Physics at the University of London and a Diploma in Crystallography from Imperial College of Science and Technology, London. From 1994 – 2001 Prof. Vrielink was an Assistant and Associate Professor at McGill University in Canada. She then continued her research as a Research Professor at the University of California, Santa Cruz. In 2007 she joined the faculty at UWA as Professor of Structural Biology
- Key research
- Dr Vrielink uses protein crystallography to study the 3D structures of macromolecules. In particular, she is interested in studying enzymes involved in redox catalysis, proteins involved in bacterial pathogenesis and proteins involved in the process of transcription elongation. Understanding the structures of these macromolecules provides important insight into their molecular and biological functions.
- In collaboration with Prof Charlene Kahler (Microbiology and Immunology), Dr. Keith Stubbs (Chemistry) and Prof Martin Scanlon (Monash University) Dr Vrielink is working in the area of endotoxin biosynthesis in Neisseria meningitidis, the causative agents of meningitis. Endotoxin molecules on these bacteria are decorated with multiple phosphoethanolamine (PEA) groups, the synthesis of which is catalyzed in part by the enzyme LptA. Inactivation of LptA increases bacterial sensitivity to defensins, suggesting that the PEA groups prevent defensin attachment to the bacterial surface. In an effort to better characterize this enzyme Dr. Vrielink has determined the three dimensional structure of the LptA enzyme. These structural studies are being correlated with functional studies carried out in Prof Kahler’s laboratory. Together with Dr. Stubbs and Prof Scanlon fragment screening and inhibitor design studies are being undertaken as steps towards development of novel antimicrobial therapeutics to treat multidrug resistance in bacteria.
- In collaboration with Dr. Grant Hartzog (University of California Santa Cruz) work is being carried out aimed at understanding the function of the ubiquitous transcription elongation factor Spt4/5 from yeast. In specific we are characterizing the RNA binding specificity of this protein and the role of the protein in transcription.
- In collaboration with Dr. Flora Meilleur (Oak Ridge National Laboratory) neutron crystallography studies are being undertaken on the flavoenzyme, cholesterol oxidase. These studies are directed at understanding the redox activity of the enzyme through characterizing the positions of hydrogen atoms within the protein during the catalytic cycle.
- Golden, E. & Vrielink, A.
Looking for hydrogen atoms: Neutron crystallography provides novel insights into protein structure and function.
Australian Journal of Chemistry, in press, (2014).
Piek, S., Wang, Z., Ganguly, J., Bartley, S.N., Shakeel, M., Anandan, A., Stubbs, K.A., Scanlon, M.J., Vrielink, A., Azadi, P., Carlson, R.W. & Kahler, C.M.
The role of oxidoreductases in determining the function of the neisserial lipid a phosphoethanolamine transferase required for resistance to polymyxin.
PLoS One, 9, e106513 (2014).
Smith, N.E., Vrielink, A., Attwood, P.V. & Corry, B.
Binding and channeling of alternative substrates in the enzyme DmpFG: a molecular dynamics study.
Biophysical Journal, 106, 1681-1690.(2014).
Blythe A., Gunasekara S., Walshe J., Mackay J.P., Hartzog G.A. & Vrielink A.
Ubiquitin fusion constructs allow the expression and purification of multi-KOW domain complexes of the Saccharomyces cerevisiae transcription elongation factor Spt4/5.
Protein Expression and Purification, 100, 54-60, (2014).
Panigrahi, R., Whelan, J. & Vrielink, A.
Exploring ligand recognition, selectivity and dynamics of TPR domains of chloroplast Toc64 and mitochondria Om64 from Arabidopsis thaliana.
Journal of Molecular Recognition, 27, 402-414, (2014).
Panigrahi, R., Adina-Zada, A., Whelan, J., & Vrielink, A.
Ligand recognition by the TPR domain of the import factor Toc64 from Arabidopsis thaliana.
PLoS One. 8, e83461, (2013).
Wanty C, Anandan A, Piek S, Walshe J, Ganguly J, Carlson RW, Stubbs KA, Kahler CM, Vrielink A.
The Structure of the Neisserial Lipooligosaccharide Phosphoethanolamine Transferase A (LptA) Required for Resistance to Polymyxin.
Journal of Molecular Biology, 425, 3389-3402, (2013)
Smith NE, Tie WJ, Flematti GR, Stubbs KA, Corry B, Attwood PV, Vrielink A.
Mechanism of the dehydrogenase reaction of DmpFG and analysis of inter-subunit channeling efficiency and thermodynamic parameters in the overall reaction.
International Journal of Biochemistry and Cell Biology, 45, 1878-1885, (2013)
Golden E, Paterson R, Tie WJ, Anandan A, Flematti G, Molla G, Rosini E, Pollegioni L, Vrielink A.
Structure of a class III engineered cephalosporin acylase: comparisons with class I acylase and implications for differences in substrate specificity and catalytic activity.
Biochemical Journal, 451, 217-226, (2013)
Anandan A, Piek S, Kahler CM, Vrielink A.
Cloning, expression, purification and crystallization of an endotoxin-biosynthesis enzyme from Neisseria meningitidis.
Acta Crystallographica Section F Structural Biology and Crystallization Communications, 68, 1494-1497, (2012)
Smith NE, Vrielink A, Attwood PV, Corry B.
Biological channeling of a reactive intermediate in the bifunctional enzyme DmpFG.
Biophysical Journal, 102, 868-877, (2012)
Kang TS, Georgieva D, Genov N, Murakami MT, Sinha M, Kumar RP, Kaur P, Kumar S, Dey S, Sharma S, Vrielink A, Betzel C, Takeda S, Arni RK, Singh TP, Kini RM.
Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis.
FEBS Journal, 278, 4544-4576, (2011)
Carrie C, Giraud E, Duncan O, Xu L, Wang Y, Huang S, Clifton R, Murcha M, Filipovska A, Rackham O, Vrielink A, Whelan J.
Conserved and novel functions for Arabidopsis thaliana MIA40 in assembly of proteins in mitochondria and peroxisomes.
Journal of Biological Chemistry, 285, 36138-36148, (2010)
Anandan A, Vallet C, Coyle T, Moustafa IM, Vrielink A.
Crystallization and preliminary diffraction analysis of an engineered cephalosporin acylase.
Acta Crystallographica Section F Structural Biology and Crystallization Communications, 66, 808-810, (2010)
Gunasekara S, Vrielink A, Stubbs KA.
Preliminary studies into the inhibition of the cholesterol alpha-glucosyltransferase from Helicobacter pylori using azasugars.
Carbohydrate Research, 345, 960-964 (2010)
Cholesterol oxidase: Structure and function.
Subcellular Biochemistry. 51, 137-158 (2010)
Lyubimov, A.Y. Chen, L. Sampson, N. S. & Vrielink, A.
A hydrogen bonding network is important for oxidation and isomerization in the reaction catalyzed by cholesterol oxidase.
Acta Crystallographica Section D. 65, pp 1222-1231 (2009)
Vrielink, A. & Ghisla, S.
Cholesterol oxidase: Biochemistry and structural features.
FEBS Journal, 276, pp 6826-6843 (2009)
Chen, L., Lyubimov, A., Brammer, L., Vrielink, A., Sampson, N.S. The binding and release of oxygen and hydrogen peroxide are directed by a hydrophobic tunnel in cholesterol oxidase, Biochemistry, 47: pp 5368-5377 (2008)
Lyubimov, A.Y., Heard, K., Tang, H., Sampson, N.S., Vrielink, A. Distortion of flavin geometry linked to ligand binding in cholesterol oxidase. Protein Science, 16: pp 2647-2656 (2007)
Moustafa, I. Foster, S. Lyubimov, A. Y., Vrielink, A. Crystal structure of LAAO from Calloselasma rhodostoma with its substrate and substrate analogue: impacts on the mechanism,
Journal of Molecular Biology, 364: pp 991-1002 (2006)
Lim, L., Guinn, N., Molla, G., Ghisla, S., Pollegioni, L., Vrielink, A. Structural and kinetic analysis of the H121A mutant of cholesterol oxidase, Biochemical Journal, 400: pp 13-22 (2006)
Lyubimov, A.Y. Lario, P.I., Moustafa,, I., Vrielink, A. Atomic resolution crystallography reveals how changes in pH shape the protein microenvironment, Nature Chemical Biology, 2: pp 259-264 (2006)
Vrielink, A., Lario, P.I., Lyubimov, A.Y. The crystal structure of cholesterol oxidase at atomic resolution: A study of the catalytic mechanism. in: 'Flavins and Flavoproteins 2005, (Eds T. Nishino et al.) ARchiTect Inc. Tokyo pp 71-80 (2005)
Lario, P.I., Sampson, N., Vrielink, A. Sub-atomic Resolution Crystal Structure of Cholesterol Oxidase: What Atomic Resolution Crystallography Reveals about Enzyme Mechanism and the Role of the FAD Cofactor in Redox Activity, Journal of Molecular Biology, 326: pp 1635-50 (2003)
Lario, P.I., Vrielink, A. Atomic Resolution Density Maps Of the Backbone Carbonyl Groups Reveal Secondary Structure Dependent Differences in Electronic Distribution, Journal of the American Chemical Society, 125: pp 12787-94 (2003)
Manjasetty, B.A., Powlowski, J., Vrielink, A. Crystal structure of a bifunctional aldolase-dehydrogenase: sequestering a reactive and volatile intermediate, Proceedings of the Natural Academy of Sciences U S A., 100: pp 6992-6997 (2003)
Sampson, N.S., Vrielink, A. Cholesterol Oxidases: A Study of Nature's Approach to Protein Design, Accounts of Chemical Research, 36: pp 713-722 (2003)
Vrielink, A., Sampson, N.S. Sub-Ångstrom Resolution Enzyme X-ray Structures: Is Seeing Believing? Current Opinion in Structural Biology, 13: pp 709-715 (2003)
Gao, Y., Vrielink, A., MacKenzie, R., Sztul, E. Formiminotransferase cyclodeaminase modulates the vimentin intermediate filament cytoskeleton by cross-linking vimentin fibers and by inhibiting filament assembly, European Journal of Cell Biology, 81: pp 391-401 (2002)
Burns, C.S., Aronoff-Spencer, E., Durham, C.M., Lario, P., Avedievich, N.I., Antholine, W.E., Olmstead, M.M., Vrielink, A., Gerfen, G.J., Peisach, J., Scott, W.G., Millhauser, G.L. Molecular features of the copper binding sites in the octarepeat domain of the prion protein, Biochemistry, 41: pp 2991-4001 (2002)
Ye, Y., Sampson, N.S., Vrielink, A., Lario, P.I. The presence of a hydrogen bond between asparagine 485 and the pi system of FAD modulates the redox potential in the reaction catalyzed by cholesterol oxidase, Biochemistry, 40: pp 13779-13787 (2001)
Geyer, A., Fitzpatrick, T.B., Pawelek, P., Kitzing, K., Vrielink, A., Ghisla, S. Macheroux, P. Structure and characterization of the glycan moiety of L-amino acid oxidase from the
malayan pit viper Calloselasma rhodostoma. European Journal of Biochemistry, 268: pp 4044-53 (2001)
Lario, P.I., Bobechko, B., Bateman, K., Vrielink, A., Huang, Z. The effect of serine phosphorylation on the PDE4A catalytic domain, Archives of Biochemistry and Biophysics, 394: pp 54-60 (2001)
Coulombe, R., Yue, K.Q., Ghisla, S., Vrielink, A. Oxygen access to the active site of cholesterol oxidase through a narrow channel is gated by an Arg-Glu pair, Journal of Biological Chemistry, 276: pp 30435-30441 (2001)
Zhang, L., Ahvazi, B., Szittner, R., Vrielink, A., Meighen, E. Differences in nucleotide specificity and catalytic mechanism between Vibrio harveyi aldehyde dehydrogenase and other members of the aldehyde dehydrogense superfamily, Chemico-Biological Interactions, 130-132: pp 29-38 (2001)
Manjasetty, B.A., Croteau, N., Powlowski, J., Vrielink, A. Crystallization and preliminary x-ray analysis of dmpFG-encoded 4-hydroxy-2-ketovalerate aldolase-aldehyde dehydrogenase (acylating) from Pseudomonas sp. Strain CF600, Acta Ctrystallographica D, 57: pp 582-585 (2001)
Pawelek, P., Cheah, J., Coulombe, R., Macheroux, P., Ghisla, S., Vrielink, A. The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site, EMBO Journal, 19: pp 4204-4215 (2000)
Ahvazi, B., Coulombe, R. Delarge, M., Zhang, L., Vedadi, M., Meighen, E., Vrielink, A. Crystal structure of the NADP+ dependant aldehyde dehydrogenase from Vibrio harveyi.
Structural implications for cofactor specificity and affinity, Biochemical Journal 349: pp 853- 861 (2000)
Kohls, D., Sulea, T., Purisima, E., MacKenzie, R., Vrielink, A. The crystal structure of the formiminotransferase domain of formiminotransferase-Cyclodeaminase: Implications for substrate channeling in a bifunctional enzyme, Structure, 8: pp 35-46 (2000)
Yue, K.Q., Kass, I.J., Sampson, N.S., Vrielink, A. Crystal Structure Determination of Cholesterol Oxidase from Streptomyces and Characterization of Key Active Site Mutants,
Biochemistry, 38: pp 4277-4286 (1999)
- Roles, responsibilities and expertise
- Head of Discipline (Biochemistry & Molecular Biology)
- Funding received
- Raine Medical Research Foundation Priming Grant
National Health and Medical Research Council Project Grant
Australian Research Council Large Equipment and Infrastructure Fund Grants
- Australian Society for Biochemistry and Molecular Biology
Asian Crystallographic Society (Web Secretary)
Society of Crystallographers of Australia and New Zealand (Vice President)
International Union of Crystallographers
- BIOC3002 (Unit Co-ordinator) Structural and Functional Biochemistry
BIOC3001 - Molecular Biology
BIOC3005 - Cellular Biochemistry
BIOC2002 - Biochemical Regulation of Cell Function
- Current external positions
- editorial Board Member - Journal of Biological Chemistry
- Current projects
Prof Grant Hartzog, University of California, Santa Cruz
Dr. Keith Stubbs, Chemistry, UWA; Prof Barry Marshall, Microbiology, UWA
Prof Charlene Kahler, Microbiology, UWA
Dr. Flora Meilleur, Oak Ridge National Laboratory, USA
- Research profile
Research profile and publications