Vrielink, Alice - University of Western Australia - School of Chemistry and Biochemistry

研究领域

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.

近期论文

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Blythe, A.J., Yazar-Klosinski, B., Webster, M.W., Chen, E., Vandevenne, M., Bendak, K., Mackay, J.P., Hartzog, G.A., Vrielink, A. 2016, 'The yeast transcription elongation factor Spt4/5 is a sequence-specific RNA binding protein', Protein Science, pp. 1710-1721. Detail Zarychta, B., Lyubimov, A.Y., Ahmed, M.M., Munshi, P., Guillot, B., Vrielink, A., Jelsch, C. 2015, 'Cholesterol oxidase: Ultrahigh-resolution crystal structure and multipolar atom model-based analysis', Acta Crystallographica Section D: Biological Crystallography, 71, pp. 954-968. Detail Golden, E., Attwood, P.V., Duff, A.P., Meilleur, F., Vrielink, A. 2015, 'Production and characterization of recombinant perdeuterated cholesterol oxidase', Analytical Biochemistry, 485, pp. 102-108. Detail Panigrahi, R., Kubiszewski-Jakubiak, S., Whelan, J., Vrielink, A. 2015, 'The design and structure of outer membrane receptors from peroxisomes, mitochondria, and chloroplasts', Structure, 23, 10, pp. 1783-1800. Detail Panigrahi, R.R., Whelan, J.M., Vrielink, A. 2014, 'Exploring ligand recognition, selectivity and dynamics of TPR domains of chloroplast Toc64 and mitochondria Om64 from Arabidopsis thaliana', Journal of Molecular Recognition, 27, 6, pp. 402-414. Detail Smith, N.E., Vrielink, A., Attwood, P.V., Corry, B. 2014, 'Binding and channeling of alternative substrates in the enzyme DmpFG: A molecular dynamics study', Biophysical Journal, 106, 8, pp. 1681-1690. Detail Blythe, A., Gunasekara, S.D., Walshe, J., Mackay, J.P., Hartzog, G.A., Vrielink, A. 2014, '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, pp. 54-60. Detail Golden, E.B., Karton, A., Vrielink, A. 2014, 'High-resolution structures of cholesterol oxidase in the reduced state provide insights into redox stabilization', ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 70, 12, pp. 3155-3166. Detail Golden, E.A., Vrielink, A. 2014, 'Looking for hydrogen atoms: Neutron crystallography provides novel insights into protein structure and function', Australian Journal of Chemistry, 67, 12, pp. 1751-1762. Detail Piek, S.H., Wang, Z., Ganguly, J., Lakey, A.M., Bartley, S.N., Mowlaboccus, S., Anandan, A., Stubbs, K.A., Scanlon, M.J., Vrielink, A., Azadi, P., Carlson, R.W., Kahler, C. 2014, 'The Role of Oxidoreductases in Determining the Function of the Neisserial Lipid A Phosphoethanolamine Transferase Required for Resistance to Polymyxin', PLoS ONE, 9, 9, pp. e106513. Detail Wanty, C., Anandan, A., Piek, S., Walshe, J., Ganguly, J., Carlson, R.W., Stubbs, K.A., Kahler, C.M., Vrielink, A. 2013, 'The structure of the neisserial lipooligosaccharide phosphoethanolamine transferase A (LptA) required for resistance to polymyxin', Journal of Molecular Biology, 425, 18, pp. 3389-3402. Detail Golden, E., Paterson, R., Tie, W.J., Anandan, A., Flematti, G., Molla, G., Rosini, E., Pollegioni, L., Vrielink, A. 2013, '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, 2, pp. 217 - 226. Detail Smith, N.E., Tie, W.J., Flematti, G.R., Stubbs, K.A., Corry, B., Vrielink, A., Attwood, P.V. 2013, '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 & CELL BIOLOGY, 45, 8, pp. 1878-1885. Detail Panigrahi, R., Adina-Zada, A., Whelan, J., Vrielink, A. 2013, 'Ligand Recognition by the TPR Domain of the Import Factor Toc64 from Arabidopsis thaliana', PLOS ONE, 8, 12, pp. 15pp. Detail Smith, N.E., Vrielink, A., Attwood, P.V., Corry, B. 2012, 'Biological Channeling of a Reactive Intermediate in the Bifunctional Enzyme DmpFG', BIOPHYSICAL JOURNAL, 102, pp. 868-877. Detail Anandan, A., Piek, S., Kahler, C.M., Vrielink, A. 2012, 'Cloning, expression, purification and crystallization of an endotoxin-biosynthesis enzyme from Neisseria meningitidis', ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS, 68, pp. 1494-1497. Detail Kang, T.S., Georgieva, D., Genov, N., Murakami, M.T., Sinha, M., Kumar, R.P., Kaur, P., Kumar, S., Dey, S., Sharma, S., Vrielink, A., Betzel, C., Takeda, S., Arni, R.K., Singh, T.P., Kini, R.M. 2011, 'Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis', FEBS JOURNAL, 278, pp. 4544-4576. Detail GUNASEKARA, S., VRIELINK, A., STUBBS, K.A. 2010, 'Preliminary studies into the inhibition of the cholesterol α-glucosyltransferase from Helicobacter pylori using azasugars', Carbohydrate Research, 345, pp. 960-964. Detail ANANDAN, A., VALLET, C., COYLE, T.B., MOUSTAFA, I.M., VRIELINK, A. 2010, 'Crystallization and preliminary diffraction analysis of an engineered cephalosporin acylase', Acta Crystallographica Section F: Structural Biology and Crystallization Communications, F66, pp. 808-810. Detail CARRIE, C., GIRAUD, E., DUNCAN, O., XU, L., WANG, Y., HUANG, S.B., CLIFTON, R., MURCHA, M., FILIPOVSKA, A., RACKHAM, O., VRIELINK, A., WHELAN, J. 2010, 'Conserved and Novel Functions for Arabidopsis thaliana MIA40 in Assembly of Proteins in Mitochondria and Peroxisomes', JOURNAL OF BIOLOGICAL CHEMISTRY, 285, 46, pp. 36138-36148. Detail