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User:Lynne Howell

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Lynne Howell obtained an undergraduate degree in Biophysics from the University of Leeds in 1983 and a Ph.D. in Crystallography from the University of London under the guidance of Prof. Dame Jane Goodfellow. She spent three years as a postdoctoral fellow with Professor Gregory Petsko at the Massachusetts Institute of Technology before moving to Paris to study with Dr. Roberto Poljak and Dr. André Menez at the Institut Pasteur. After a year as a staff scientist in Paris, Dr. Howell joined The Hospital of Sick Children in Toronto in late 1991 and was cross appointed to the University of Toronto shortly thereafter. She’s a recipient of a Canada Research Chair in Structural Biology and her research is focused on microbial biofilm formation, specifically understanding at the molecular level the exopolysaccharide biosynthetic systems of various bacteria and fungi (more information can be found on the laboratory webpage). This work has involved collaborations with Prof. Anthony Clarke, Prof. Mark Nitz, Prof. Jeroen Codée, Prof. John Klassen, Prof. Don Sheppard and Prof. Joel Weadge, among others.

Her lab has determined the crystal structures of multiple carbohydrate active enzymes including (but not limited to):

  • GH39 Pseudomonas aeruginosa PslG, PSL polysaccharide hydrolase [1]
  • GH47 Penicillium citrinum α-1,2-mannosidase [2]
  • GH114 Aspergillus fumigatus Ega3, an α-1,4-galactosaminidase [3]
  • GH135 Aspergillus clavatus Sph3, an α-1,4-N-acetylgalactosaminidase  [4]
  • GH153 Bordetella bronchiseptica PgaB (C-terminal domain), a poly-β-1,6-D-glucosamine hydrolase [5]
  • GH166 Pseudomonas aeruginosa PelA (N-terminal domain), α-1,4-N-acetylgalactosaminidase [6]
  • CE4 Ammonifex degensii IcaB, a poly-β-1,6-N-acetyl-D-glucosamine deacetylase [7
  • CE4 Bordetella bronchiseptica PgaB (N-terminal domain), a poly-β-1,6-N-acetyl-D-glucosamine deacetylase [8]
  • CE4/GH153 Escherichia coli PgaB, a poly-β-1,6-D-glucosamine deacetylase and hydrolase [9]
  • CE18 and CBM87 Aspergillus fumigatus Agd3, an α-1,4-N-acetylgalactosaminidase deacetylase [10
  • PL5 Pseudomonas aeruginosa AlgL, (no associated paper)
  • PL7 Klebsiella pneumoniae Alginate lyase, (no associated paper)
  • GT15 Saccharomyces cerevisiae ⍺-1,2-monnosyltransferase complex Kre2p/Mnt1p [11]
  • Pseudomonas syringae AlgG, β-D-mannuronate (alginate) C5-epimerase [12]
  • Pseudomonas putida AlgJ, involved in alginate O-acetylation [13]
  • Pseudomonas aeruginosa AlgX, alginate O-acetylase [14]
  • Pseudomonas protegens PelX, a C-4 epimerase that interconverts UDP-GalNAc and UDP-GlcNAc [15]
  • Bacillus cereus PatB1, peptidoglycan O-acetylase [16]
  • Streptococcus pneumoniae OatA, peptidoglycan O-acetylase [17]
  • Staphylococcus aureus OatA, peptidoglycan O-acetylase [18]

  1. Baker P, Whitfield GB, Hill PJ, Little DJ, Pestrak MJ, Robinson H, Wozniak DJ, and Howell PL. (2015) Characterization of the Pseudomonas aeruginosa Glycoside Hydrolase PslG Reveals That Its Levels Are Critical for Psl Polysaccharide Biosynthesis and Biofilm Formation. J Biol Chem. 290, 28374-87. DOI:10.1074/jbc.M115.674929 | PubMed ID:26424791 | HubMed [Baker2015]
  2. Lobsanov YD, Vallée F, Imberty A, Yoshida T, Yip P, Herscovics A, and Howell PL. (2002) Structure of Penicillium citrinum alpha 1,2-mannosidase reveals the basis for differences in specificity of the endoplasmic reticulum and Golgi class I enzymes. J Biol Chem. 277, 5620-30. DOI:10.1074/jbc.M110243200 | PubMed ID:11714724 | HubMed [Lobsanov2002]
  3. Bamford NC, Le Mauff F, Subramanian AS, Yip P, Millán C, Zhang Y, Zacharias C, Forman A, Nitz M, Codée JDC, Usón I, Sheppard DC, and Howell PL. (2019) Ega3 from the fungal pathogen Aspergillus fumigatus is an endo-α-1,4-galactosaminidase that disrupts microbial biofilms. J Biol Chem. 294, 13833-13849. DOI:10.1074/jbc.RA119.009910 | PubMed ID:31416836 | HubMed [Bamford2019]
  4. Bamford NC, Snarr BD, Gravelat FN, Little DJ, Lee MJ, Zacharias CA, Chabot JC, Geller AM, Baptista SD, Baker P, Robinson H, Howell PL, and Sheppard DC. (2015) Sph3 Is a Glycoside Hydrolase Required for the Biosynthesis of Galactosaminogalactan in Aspergillus fumigatus. J Biol Chem. 290, 27438-50. DOI:10.1074/jbc.M115.679050 | PubMed ID:26342082 | HubMed [Bamford2015]
  5. Little DJ, Pfoh R, Le Mauff F, Bamford NC, Notte C, Baker P, Guragain M, Robinson H, Pier GB, Nitz M, Deora R, Sheppard DC, and Howell PL. (2018) PgaB orthologues contain a glycoside hydrolase domain that cleaves deacetylated poly-β(1,6)-N-acetylglucosamine and can disrupt bacterial biofilms. PLoS Pathog. 14, e1006998. DOI:10.1371/journal.ppat.1006998 | PubMed ID:29684093 | HubMed [Little2018]
  6. Le Mauff F, Bamford NC, Alnabelseya N, Zhang Y, Baker P, Robinson H, Codée JDC, Howell PL, and Sheppard DC. (2019) Molecular mechanism of Aspergillus fumigatus biofilm disruption by fungal and bacterial glycoside hydrolases. J Biol Chem. 294, 10760-10772. DOI:10.1074/jbc.RA119.008511 | PubMed ID:31167793 | HubMed [LeMauff2019]
  7. Little DJ, Bamford NC, Pokrovskaya V, Robinson H, Nitz M, and Howell PL. (2014) Structural basis for the De-N-acetylation of Poly-β-1,6-N-acetyl-D-glucosamine in Gram-positive bacteria. J Biol Chem. 289, 35907-17. DOI:10.1074/jbc.M114.611400 | PubMed ID:25359777 | HubMed [Little2014]
  8. Little DJ, Milek S, Bamford NC, Ganguly T, DiFrancesco BR, Nitz M, Deora R, and Howell PL. (2015) The protein BpsB is a poly-β-1,6-N-acetyl-D-glucosamine deacetylase required for biofilm formation in Bordetella bronchiseptica. J Biol Chem. 290, 22827-40. DOI:10.1074/jbc.M115.672469 | PubMed ID:26203190 | HubMed [Little2015]
  9. Little DJ, Li G, Ing C, DiFrancesco BR, Bamford NC, Robinson H, Nitz M, Pomès R, and Howell PL. (2014) Modification and periplasmic translocation of the biofilm exopolysaccharide poly-β-1,6-N-acetyl-D-glucosamine. Proc Natl Acad Sci U S A. 111, 11013-8. DOI:10.1073/pnas.1406388111 | PubMed ID:24994902 | HubMed [Little2014b]
  10. Bamford NC, Le Mauff F, Van Loon JC, Ostapska H, Snarr BD, Zhang Y, Kitova EN, Klassen JS, Codée JDC, Sheppard DC, and Howell PL. (2020) Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation. Nat Commun. 11, 2450. DOI:10.1038/s41467-020-16144-5 | PubMed ID:32415073 | HubMed [Bamford2020]
  11. Lobsanov YD, Romero PA, Sleno B, Yu B, Yip P, Herscovics A, and Howell PL. (2004) Structure of Kre2p/Mnt1p: a yeast alpha1,2-mannosyltransferase involved in mannoprotein biosynthesis. J Biol Chem. 279, 17921-31. DOI:10.1074/jbc.M312720200 | PubMed ID:14752117 | HubMed [Lobsanov2004]
  12. Wolfram F, Kitova EN, Robinson H, Walvoort MT, Codée JD, Klassen JS, and Howell PL. (2014) Catalytic mechanism and mode of action of the periplasmic alginate epimerase AlgG. J Biol Chem. 289, 6006-19. DOI:10.1074/jbc.M113.533158 | PubMed ID:24398681 | HubMed [Wolfram2014]
  13. Baker P, Ricer T, Moynihan PJ, Kitova EN, Walvoort MT, Little DJ, Whitney JC, Dawson K, Weadge JT, Robinson H, Ohman DE, Codée JD, Klassen JS, Clarke AJ, and Howell PL. (2014) P. aeruginosa SGNH hydrolase-like proteins AlgJ and AlgX have similar topology but separate and distinct roles in alginate acetylation. PLoS Pathog. 10, e1004334. DOI:10.1371/journal.ppat.1004334 | PubMed ID:25165982 | HubMed [Baker2014]
  14. Riley LM, Weadge JT, Baker P, Robinson H, Codée JD, Tipton PA, Ohman DE, and Howell PL. (2013) Structural and functional characterization of Pseudomonas aeruginosa AlgX: role of AlgX in alginate acetylation. J Biol Chem. 288, 22299-314. DOI:10.1074/jbc.M113.484931 | PubMed ID:23779107 | HubMed [Riley2013]
  15. Marmont LS, Whitfield GB, Pfoh R, Williams RJ, Randall TE, Ostaszewski A, Razvi E, Groves RA, Robinson H, Nitz M, Parsek MR, Lewis IA, Whitney JC, Harrison JJ, and Howell PL. (2020) PelX is a UDP-N-acetylglucosamine C4-epimerase involved in Pel polysaccharide-dependent biofilm formation. J Biol Chem. 295, 11949-11962. DOI:10.1074/jbc.RA120.014555 | PubMed ID:32601062 | HubMed [Marmont2020]
  16. Sychantha D, Little DJ, Chapman RN, Boons GJ, Robinson H, Howell PL, and Clarke AJ. (2018) PatB1 is an O-acetyltransferase that decorates secondary cell wall polysaccharides. Nat Chem Biol. 14, 79-85. DOI:10.1038/nchembio.2509 | PubMed ID:29083419 | HubMed [Sychantha2018]
  17. Sychantha D, Jones CS, Little DJ, Moynihan PJ, Robinson H, Galley NF, Roper DI, Dowson CG, Howell PL, and Clarke AJ. (2017) In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA). PLoS Pathog. 13, e1006667. DOI:10.1371/journal.ppat.1006667 | PubMed ID:29077761 | HubMed [Sychantha2018]
  18. Jones CS, Sychantha D, Howell PL, and Clarke AJ. (2020) Structural basis for the O-acetyltransferase function of the extracytoplasmic domain of OatA from Staphylococcus aureus. J Biol Chem. 295, 8204-8213. DOI:10.1074/jbc.RA120.013108 | PubMed ID:32350117 | HubMed [Jones2020]
All Medline abstracts: PubMed | HubMed