The University of Western Australia
W/Prof Alice Vrielink
Winthrop Professor in Structural Biology
Contact details
| Address | Biochemistry and Molecular Biology The University of Western Australia (M310) 35 Stirling Highway CRAWLEY WA 6009 Australia |
|---|---|
| Phone | 6488 3162 |
| Fax | 6488 7330 |
| alice.vrielink@uwa.edu.au | |
| Personal homepage | http://www.crystal.uwa.edu.au/px/alice/index.html |
Location
Room 431, Molecular and Chemical Sciences Building, Crawley campus
Biography
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, multifunctional enzymes involved in substrate channeling and proteins involved in the process of transcription elongation. Understanding the structures of these macromolecules provides important insight into their molecular and biological functions.
- A new project that Dr Vrielink is working on in collaboration with Dr. Charlene Kahler (Microbiology and Immunology) is in the area of endotoxin biosynthesis in Neisseria bacteria. These bacteria are 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 is determining the three dimensional structure of the LptA enzyme and will correlate the structure with functional studies carried out in Dr. Kahler’s laboratory.
- In collaboration with Prof Jim Whelan (Plant Energy Biology) Dr. Vrielink’s laboratory is pursuing structural studies of proteins involved in mitochondrial protein import. These studies are aimed at understanding the structural features that mediate recognition of molecules destined to be imported into mitochondria.
- Other collaborative studies are ongoing with Prof Arunasalam Dharmarajan, (Anatomy and Human Biology) on proteins involved in signaling pathways and implicated in cancer.
Major research interests
- Enzyme mechanism
- Protein structure and function
- Flavoenzymes
- Ultra high resolution crystallography
- Macromolecular crystallography
- Multifunctional enzymes
- Transcription factors
Qualifications
BSc MSc Calg., PhD Lond.
Publications
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 - Biological Crystallography, in press (2009).
Vrielink, A., Ghisla, S. Cholesterol oxidase: Biochemistry and structural features.
FEBS Journal, in press (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)
Acta Crystallographica Section D - Biological Crystallography, in press (2009).
Vrielink, A., Ghisla, S. Cholesterol oxidase: Biochemistry and structural features.
FEBS Journal, in press (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)
Future research
Prof Vrielink has the following student project available:
Structural and functional studies of a bifunctional enzyme involved in substrate channeling (PhD) Three year scholarship available, $22, 500 p.a. Please contact Dr Vrielink for more information.
Structural and functional studies of a bifunctional enzyme involved in substrate channeling (PhD) Three year scholarship available, $22, 500 p.a. Please contact Dr Vrielink for more information.
Funding received
Raine Medical Research Foundation Priming Grant
Memberships
Australian Society for Biochemistry and Molecular Biology
American Crystallographic Society
Protein Society
Society of Crystallographers of Australia and New Zealand
International Union of Crystallographers
American Crystallographic Society
Protein Society
Society of Crystallographers of Australia and New Zealand
International Union of Crystallographers
Teaching
BIOC3351 (Unit Co-ordinator) Molecular and Structural Biochemistry
BIOC3352 Cellular and Metabolic Biochemistry
GENE3330 Molecular Genetics and Genomics
BIOC2202 Biochemical Regulation of Cell Function
BIOC3353/3354 (Unit Co-ordinator) Molecular and Structural Biochemistry (Singapore Campus)
Honours in Biochemistry (Coordinator)
BIOC3352 Cellular and Metabolic Biochemistry
GENE3330 Molecular Genetics and Genomics
BIOC2202 Biochemical Regulation of Cell Function
BIOC3353/3354 (Unit Co-ordinator) Molecular and Structural Biochemistry (Singapore Campus)
Honours in Biochemistry (Coordinator)
Current projects
Collaborators
Prof Nicole Sampson, State University of New York and Stonybrook
Prof Loredana Pollegioni, University of Insubria, Italy
Prof Grant Hartzog, University of California, Santa Cruz
Prof Arunasalam Dharmarajan, Anatomy and Human Biology, UWA
Dr Charlie Kahler, Microbiology, UWA
Prof Jim Whelan, Plant Energy Biology, UWA
Prof Nicole Sampson, State University of New York and Stonybrook
Prof Loredana Pollegioni, University of Insubria, Italy
Prof Grant Hartzog, University of California, Santa Cruz
Prof Arunasalam Dharmarajan, Anatomy and Human Biology, UWA
Dr Charlie Kahler, Microbiology, UWA
Prof Jim Whelan, Plant Energy Biology, UWA
Research profile
