Alice Vrielink

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Alice Vrielink
Alma materUniversity of London
Scientific career
Thesis The crystal structure determination of cholesterol oxidase  (1989)
Doctoral advisor David Mervyn Blow [1]

Alice Vrielink is a structural biologist and Professor of Structural Biology in the School of Molecular Sciences at the University of Western Australia. She is known for her work determining the structures of macromolecules such as enzymes and nucleic acids.

Contents

Education

Vrielink earned a Bachelor of Science in Chemistry and Masters of Science in Physical Chemistry at the University of Calgary in Canada. [2] For her master's research she worked on ligands of angiotensin, a hormone involved in regulating blood pressure. [3] She received a PhD in 1989 from the University of London where she worked on the structure of cholesterol oxidase. [4] She also has a Diploma in Crystallography from the Imperial College of Science and Technology. [2]

Career

Vrielink was an Assistant and Associate Professor at McGill University in Canada from 1994 to 2001. [2] From 2000 until 2007 she served as a Research Professor at the University of California, Santa Cruz and then joined the faculty at University of Western Australia as Professor of Structural Biology in 2007. [2]

Vrielink was a member of the 2014 National Committee on Crystallography [5] She is a past president of the Society of Crystallographers of Australia and New Zealand (SCANZ). [6]

Research

Vrielink conducts research in protein biochemistry and crystallography with a special focus on understanding the structural determinants governing enzyme chemistry. [7] Vrielink's early research centered on the three-dimensional structure of the enzyme cholesterol oxidase first in Brevibacterium [8] [9] and then in Streptomyces. [10]

She has been involved in projects that have established the structure of compounds including L-amino-acid oxidase, [11] prions, [12] and snake venom. [13] In 2017, she mapped the molecular structure of EptA, [14] a protein that shields superbugs from antibiotics. This work has been covered by the BBC, [15] ABC, [16] Times Higher Education, [17] The West Australian, [18] and Particle. [19] Subsequent work on EptA has revealed why it may be a good target for drug development. [20] [21]

Selected publications

Related Research Articles

<span class="mw-page-title-main">Enzyme</span> Large biological molecule that acts as a catalyst

Enzymes are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called enzymology and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties.

<span class="mw-page-title-main">Rossmann fold</span>

The Rossmann fold is a tertiary fold found in proteins that bind nucleotides, such as enzyme cofactors FAD, NAD+, and NADP+. This fold is composed of alternating beta strands and alpha helical segments where the beta strands are hydrogen bonded to each other forming an extended beta sheet and the alpha helices surround both faces of the sheet to produce a three-layered sandwich. The classical Rossmann fold contains six beta strands whereas Rossmann-like folds, sometimes referred to as Rossmannoid folds, contain only five strands. The initial beta-alpha-beta (bab) fold is the most conserved segment of the Rossmann fold. The motif is named after Michael Rossmann who first noticed this structural motif in the enzyme lactate dehydrogenase in 1970 and who later observed that this was a frequently occurring motif in nucleotide binding proteins.

Catechol oxidase is a copper oxidase that contains a type 3 di-copper cofactor and catalyzes the oxidation of ortho-diphenols into ortho-quinones coupled with the reduction of molecular oxygen to water. It is present in a variety of species of plants and fungi including Ipomoea batatas and Camellia sinensis. Metalloenzymes with type 3 copper centers are characterized by their ability to reversibly bind dioxygen at ambient conditions. In plants, catechol oxidase plays a key role in enzymatic browning by catalyzing the oxidation of catechol to o-quinone in the presence of oxygen, which can rapidly polymerize to form the melanin that grants damaged fruits their dark brown coloration.

<span class="mw-page-title-main">Barnase</span> Bacterial ribonuclease protein

Barnase (a portmanteau of "BActerial" "RiboNucleASE") is a bacterial protein that consists of 110 amino acids and has ribonuclease activity. It is synthesized and secreted by the bacterium Bacillus amyloliquefaciens, but is lethal to the cell when expressed without its inhibitor barstar. The inhibitor binds to and occludes the ribonuclease active site, preventing barnase from damaging the cell's RNA after it has been synthesized but before it has been secreted. The barnase/barstar complex is noted for its extraordinarily tight protein-protein binding, with an on-rate of 108s−1M−1.

The omega loop is a non-regular protein structural motif, consisting of a loop of six or more amino acid residues and any amino acid sequence. The defining characteristic is that residues that make up the beginning and end of the loop are close together in space with no intervening lengths of regular secondary structural motifs. It is named after its shape, which resembles the upper-case Greek letter Omega (Ω).

In enzymology, a cellobiose dehydrogenase (acceptor) (EC 1.1.99.18) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Amine oxidase (copper-containing)</span>

Amine oxidase (copper-containing) (AOC) (EC 1.4.3.21 and EC 1.4.3.22; formerly EC 1.4.3.6) is a family of amine oxidase enzymes which includes both primary-amine oxidase and diamine oxidase; these enzymes catalyze the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. They act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor:

<span class="mw-page-title-main">L-amino-acid oxidase</span>

In enzymology, an L-amino acid oxidase (LAAO) (EC 1.4.3.2) is an enzyme that catalyzes the chemical reaction

A polyamine oxidase (PAO) is an enzymatic flavoprotein that oxidizes a carbon-nitrogen bond in a secondary amino group of a polyamine donor, using molecular oxygen as an acceptor. The generalized PAO reaction converts three substrates into three products. Different PAOs with varying substrate specificities exist in different organisms. Phylogenetic analyses suggest that PAOs likely evolved once in eukaryotes and diversified by divergent evolution and gene duplication events, though some prokaryotes have acquired PAOs through horizontal gene transfer.

<span class="mw-page-title-main">Diphosphomevalonate decarboxylase</span> InterPro Family

Diphosphomevalonate decarboxylase (EC 4.1.1.33), most commonly referred to in scientific literature as mevalonate diphosphate decarboxylase, is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">ATP citrate synthase</span> Class of enzymes

ATP citrate synthase (also ATP citrate lyase (ACLY)) is an enzyme that in animals represents an important step in fatty acid biosynthesis. By converting citrate to acetyl-CoA, the enzyme links carbohydrate metabolism, which yields citrate as an intermediate, with fatty acid biosynthesis, which consumes acetyl-CoA. In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursors of thousands of specialized metabolites, including waxes, sterols, and polyketides.

<span class="mw-page-title-main">Dipeptidase 1</span> Protein-coding gene in the species Homo sapiens

Dipeptidase 1 (DPEP1), or renal dipeptidase, is a membrane-bound glycoprotein responsible for hydrolyzing dipeptides. It is found in the microsomal fraction of the procine kidney cortex. It exists as a disulfide-linked homodimer that is glygosylphosphatidylinositol (GPI)-anchored to the renal brush border of the kidney. The active site on each homodimer is made up of a barrel subunit with binuclear zinc ions that are bridged by the Gly125 side-chain located at the bottom of the barrel.

<span class="mw-page-title-main">Tej P. Singh</span> Indian biophysicist (1944–)

Tej Pal Singh is an Indian biophysicist known for his work in the fields of rational structure-based drug design, structural biology of proteins and X-ray crystallography. He has played an active role in the development of drug design in the fields of antibacterial therapeutics, tuberculosis, inflammation, cancer and gastropathy.

<span class="mw-page-title-main">Morpheein</span> Model of protein allosteric regulation

Morpheeins are proteins that can form two or more different homo-oligomers, but must come apart and change shape to convert between forms. The alternate shape may reassemble to a different oligomer. The shape of the subunit dictates which oligomer is formed. Each oligomer has a finite number of subunits (stoichiometry). Morpheeins can interconvert between forms under physiological conditions and can exist as an equilibrium of different oligomers. These oligomers are physiologically relevant and are not misfolded protein; this distinguishes morpheeins from prions and amyloid. The different oligomers have distinct functionality. Interconversion of morpheein forms can be a structural basis for allosteric regulation, an idea noted many years ago, and later revived. A mutation that shifts the normal equilibrium of morpheein forms can serve as the basis for a conformational disease. Features of morpheeins can be exploited for drug discovery. The dice image represents a morpheein equilibrium containing two different monomeric shapes that dictate assembly to a tetramer or a pentamer. The one protein that is established to function as a morpheein is porphobilinogen synthase, though there are suggestions throughout the literature that other proteins may function as morpheeins.

<span class="mw-page-title-main">Phosphoribosylglycinamide formyltransferase</span>

Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2, 2-amino-N-ribosylacetamide 5'-phosphate transformylase, GAR formyltransferase, GAR transformylase, glycinamide ribonucleotide transformylase, GAR TFase, 5,10-methenyltetrahydrofolate:2-amino-N-ribosylacetamide ribonucleotide transformylase) is an enzyme with systematic name 10-formyltetrahydrofolate:5'-phosphoribosylglycinamide N-formyltransferase. This enzyme catalyses the following chemical reaction

Amy C. Rosenzweig is a professor of Chemistry and Molecular Biosciences at Northwestern University. She was born in 1967 in Pittsburgh, Pennsylvania. Her current research interests include structural biology and bioinorganic chemistry, metal uptake and transport, oxygen activation by metalloenzymes, and characterization of membrane protein. For her work, she has been recognized by a number of national and international awards, including the MacArthur "Genius" Award in 2003.

<span class="mw-page-title-main">Glucose-methanol-choline oxidoreductase family</span>

In molecular biology, the glucose-methanol-choline oxidoreductase family is a family of enzymes with oxidoreductase activity.

<span class="mw-page-title-main">Primary-amine oxidase</span>

Primary-amine oxidase, also known as semicarbazide-sensitive amine oxidase (SSAO), is an enzyme (EC 1.4.3.21) with the systematic name primary-amine:oxygen oxidoreductase (deaminating). This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Gideon Davies</span> Professor of Chemistry

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<span class="mw-page-title-main">Squire Booker</span> American biochemist

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References

  1. Vrielink, Alice (3 July 2014). "David Blow (1931-2004) - A Remberance" (PDF). American Crystallographic Association. Archived (PDF) from the original on 3 July 2014. Retrieved 14 October 2021.
  2. 1 2 3 4 "Researcher Profile: Professor Alice Vrielink". UWA Research Repository.
  3. Vrielink, Alice (1986). Structural and conformational energy studies of ligands of angiotensin converting enzyme and thermolysin (Thesis). Ottawa: National Library of Canada. OCLC   16710356.
  4. Vrielink, Alice; University of London (1989). The crystal structure determination of cholesterol oxidase. hdl:10044/1/47699. OCLC   1063590654.
  5. "Triennial Congress and General Assembly". Australian Academy of Science newsletter.
  6. Vrielink, Alice (2016). "From the President" (PDF). Scanz Newsletter. Retrieved 7 February 2018.
  7. Ducy, Liam. "UWA celebrates Australian link in scientific breakthrough". WAToday, August 20, 2014.
  8. Li, Jiayao; Vrielink, Alice; Brick, Peter; Blow, David M. (26 January 1993). "Crystal structure of cholesterol oxidase complexed with a steroid substrate: Implications for flavin adenine dinucleotide dependent alcohol oxidases". Biochemistry. 32 (43): 11507–11515. doi:10.1021/bi00094a006. ISSN   0006-2960. PMID   8218217.
  9. Vrielink, Alice; Lloyd, Lesley F; Blow, David M (5 June 1991). "Crystal structure of cholesterol oxidase from Brevibacterium sterolicum refined at 1.8 Å resolution". Journal of Molecular Biology. 219 (3): 533–554. doi:10.1016/0022-2836(91)90192-9. ISSN   0022-2836. PMID   2051487.
  10. Yue, Q. Kimberley; Kass, Ignatius J.; Sampson, Nicole S.; Vrielink, Alice (1 April 1999). "Crystal Structure Determination of Cholesterol Oxidase from Streptomyces and Structural Characterization of Key Active Site Mutants". Biochemistry. 38 (14): 4277–4286. doi:10.1021/bi982497j. ISSN   0006-2960. PMID   10194345.
  11. Pawelek, P. D. (15 August 2000). "The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site". The EMBO Journal. 19 (16): 4204–4215. doi:10.1093/emboj/19.16.4204. PMC   302035 . PMID   10944103.
  12. Burns, Colin S.; Aronoff-Spencer, Eliah; Dunham, Christine M.; Lario, Paula; Avdievich, Nikolai I.; Antholine, William E.; Olmstead, Marilyn M.; Vrielink, Alice; Gerfen, Gary J.; Peisach, Jack; Scott, William G. (1 March 2002). "Molecular Features of the Copper Binding Sites in the Octarepeat Domain of the Prion Protein". Biochemistry. 41 (12): 3991–4001. doi:10.1021/bi011922x. ISSN   0006-2960. PMC   2905306 . PMID   11900542.
  13. Kang, Tse Siang; Georgieva, Dessislava; Genov, Nikolay; Murakami, Mário T.; Sinha, Mau; Kumar, Ramasamy P.; Kaur, Punit; Kumar, Sanjit; Dey, Sharmistha; Sharma, Sujata; Vrielink, Alice (2011). "Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis". The FEBS Journal. 278 (23): 4544–4576. doi: 10.1111/j.1742-4658.2011.08115.x . ISSN   1742-4658. PMID   21470368. S2CID   40199362.
  14. Anandan, Anandhi; Evans, Genevieve L.; Condic-Jurkic, Karmen; O’Mara, Megan L.; John, Constance M.; Phillips, Nancy J.; Jarvis, Gary A.; Wills, Siobhan S.; Stubbs, Keith A.; Moraes, Isabel; Kahler, Charlene M.; Vrielink, Alice (28 February 2017). "Structure of a lipid A phosphoethanolamine transferase suggests how conformational changes govern substrate binding". Proceedings of the National Academy of Sciences. 114 (9): 2218–2223. doi: 10.1073/pnas.1612927114 . ISSN   0027-8424. PMC   5338521 . PMID   28193899.
  15. Dunlop, Greg (15 February 2017). "Antibiotic resistance: Scientists 'unmask' superbug-shielding protein". BBC News. Retrieved 7 February 2018.
  16. Wildie, Tom (14 February 2017). "Australian scientists make breakthrough in fight against superbugs". ABC News. Retrieved 7 February 2018.
  17. "Stopping the rise of the superbug". Times Higher Education. Archived from the original on 8 February 2018. Retrieved 7 February 2018.
  18. O'Leary, Cathy (14 February 2017). "UWA breakthrough in superbug battle". The West Australian. Retrieved 7 February 2018.
  19. Mitchell, Samille (14 March 2017). "WA Scientists Fight Deadly Superbugs". Particle.
  20. Kahler, Charlene M.; Nawrocki, K. L.; Anandan, A.; Vrielink, Alice; Shafer, William M. (2018). "Structure-Function Relationships of the Neisserial EptA Enzyme Responsible for Phosphoethanolamine Decoration of Lipid A: Rationale for Drug Targeting". Frontiers in Microbiology. 9: 1922. doi: 10.3389/fmicb.2018.01922 . ISSN   1664-302X. PMC   6111236 . PMID   30186254.
  21. Anandan, Anandhi; Dunstan, Nicholas W.; Ryan, Timothy M.; Mertens, Haydyn D. T.; Lim, Katherine Y. L.; Evans, Genevieve L.; Kahler, Charlene M.; Vrielink, Alice (1 September 2021). "Conformational flexibility of EptA driven by an interdomain helix provides insights for enzyme–substrate recognition". IUCrJ. 8 (5): 732–746. doi:10.1107/S2052252521005613. ISSN   2052-2525. PMC   8420757 . PMID   34584735.