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Research Group Arwen Pearson

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Research in my group is focussed on understanding how macromolecular structure leads to function. Biological macromolecules are not static and therefore to understand how they work we need to visualise them with high resolution in both space and time. To address this challenge my group is developing a suite of methodologies for time-resolved structure determination.

Current major projects include:

  • Development of time-resolved X-ray crystallography and SAXS
  • Mechanistic enzymology
  • ssRNA virus capsid structure, assembly and disassembly
  • Using single crystal UV/Vis, Raman and THz spectroscopy to study protein dynamics and function

This means developing:

1) novel data collection methodologies that will allow us to carry out fast time-resolved structural studies on standard monochromatic beamlines,

2) a library of photocaging chemistries that can be used to simultaneously trigger a reaction in the crystalline state,

3) complementary solution phase experiments to probe large scale conformational rearrangements and

4) THz time-domain spectroscopy as a tool to probe global dynamic behaviour.

 If you’re interested in joining us, please contact

Prof. Dr. Arwen Pearson
Bldg. 99 (CFEL), Rm 1.096
Luruper Chausse 149
22761 Hamburg
Phone: +49-40-8998 6650
Mail: arwen.pearson@cfel.de

 

Publication List

Levantino M, Yorke BA, Monteiro DCF, Cammarata M, Pearson AR Using synchrotrons and XFELs for time-resolved X-ray crystallography and solution scattering experiments on biomolecules, Curr. Opin. Struct. Biol. 35 in press, 2015

Mueller C, Marx A, Epp SW, Zhong Y, Kuo A, Balo AR, Soman J, Schotte F, Lemke HT, Owen RL, Pai EF, Pearson AR, Olson JS, Anfinrud PA, Ernst OP, Miller RJD Fixed target matrix for femtosecond time-resolved and in situ serial micro-crystallography, Structural Dynamics 2 054302, 2015

Monteiro DCF, Patel V, Bartlett CP, Nozaki S, Grant TD, Gowdy JA, Thompson GS, Kalverda AP, Snell EH, Niki H, Pearson AR, Webb ME The structure of the PanD/PanZ protein complex reveals negative feedback regulation of pantothenate biosynthesis by Coenzyme A, Chemistry & Biology 22 492-503, 2015

Gaule TG, Smith MA, Pearson AR, Knowles PF, McPherson MJ Probing the molecular mechanisms in copper amine oxidase by generating heterodimers. ChemBioChem 16 559-564, 2015

Gray A, Harlen OG, Harris SA, Khalid S, Leung YM, Lonsdale R, Mulholland AJ, Pearson AR, Read DJ, Richardson RA In pursuit of an accurate spatial and temporal model of biomolecules at the atomistic level: a perspective on computer simulation. Acta Cryst. 71 162-171, 2015

Yorke BA, Beddard GS, Owen RL, Pearson AR Time-resolved crystallography using the Hadamard transform. Nature Methods 11 1131-1134, 2014
DOI:10.1038/nmeth.3139

Vella M, Hunter T, Farrugia C, Pearson AR, Hunter G Purification and characterisation of xanthine oxidoreductase from local bovids in Malta Advances in Enzyme Research 2 54-63, 2014
DOI:10.4236/aer.2014.21006

Foster TL; Thompson GS; Kalverda AP; Kankanala J; Bentham M; Wetherill LF; Thompson J; Barker AM; Clarke D; Noerenberg M; Pearson AR; Rowlands DJ; Homans SW; Harris M; Foster R; Griffin S Structure-guided design affirms inhibitors of hepatitis C virus p7 as a viable class of antivirals targeting virion release. Hepatology 59 408-422, 2014
DOI:10.1002/hep.26685

Tych KM; Wood CD; Burnett AD; Pearson AR; Davies AG; Linfield EH; Cunningham JE Probing temperature- and solvent-dependent protein dynamics using terahertz time-domain spectroscopy Journal of Applied Crystallography 47 146-153, 2014
DOI:10.1107/S1600576713029506

Bolze CS; Helbling RE; Furrer J; Cascella M; Stocker A; Owen RL; Pearson AR; Pompidor G; Dworkowski F; Fuchs MR; Golczak M; Palczewski K Human cellular retinaldehyde-binding protein has secondary thermal 9-cis-retinal isomerase activity Journal of the American Chemical Society 136 137-146, 2014
DOI:10.1021/ja411366w

Daniels AD; Campeotto I; van der Kamp MW; Bolt AH; Trinh CH; Phillips SE; Pearson AR; Nelson A; Mulholland AJ; Berry A Reaction Mechanism of N-Acetylneuraminic Acid Lyase Revealed by a Combination of Crystallography, QM/MM Simulation, and Mutagenesis. ACS Chem Biol -, 2014
DOI:10.1021/cb500067z

Bakker SE; Groppelli E; Pearson AR; Stockley PG; Rowlands DJ; Ranson NA The limits of structural plasticity in a picornavirus capsid revealed by a massively expanded equine rhinitis A virus particle. J Virol -, 2014
DOI:10.1128/JVI.01979-13

Webb ME; Yorke BA; Kershaw T; Lovelock S; Lobley CM; Kilkenny ML; Smith AG; Blundell TL; Pearson AR; Abell C Threonine 57 is required for the post-translational activation of Escherichia coli aspartateα-decarboxylase. Acta Crystallogr D Biol Crystallogr 70 1166-1172, 2014
DOI:10.1107/S1399004713034275

Yuzugullu Y; Trinh CH; Smith MA; Pearson AR; Sutay Kocabas D; Phillips SEV; Bakir U; Ogel ZB; McPherson MJ Crystal structure, recombinant expression and mutagenesis studies of the bifunctional catalase-phenol oxidase from Scytalidium thermophilum Acta Crystallographica Section D: Biological Crystallography 69 398-408, 2013

Timms N; Windle CL; Polyakova A; Ault JR; Trinh CH; Pearson AR; Nelson A; Berry A Structural insights into the recovery of aldolase activity in N-acetylneuraminic acid lyase by replacement of the catalytically active lysine withγ-thialysine by using a chemical mutagenesis strategy. Chembiochem 14 474-481, 2013
DOI:10.1002/cbic.201200714

Ford RJ; Barker AM; Bakker SE; Coutts RH; Ranson NA; Phillips SE; Pearson AR; Stockley PG Sequence-specific, RNA-protein interactions overcome electrostatic barriers preventing assembly of satellite tobacco necrosis virus coat protein. J Mol Biol 425 1050-1064, 2013
DOI:10.1016/j.jmb.2013.01.004

Stockley PG; Barker AM; Borodavka A; Ford RJ; Pearson AR; Ranson NA; Tuma R; Twarock R; Dykeman E; Phillips SEV; Bakker SE Packaging signals in single-stranded RNA viruses: nature’s alternative to a purely electrostatic assembly mechanism Journal of Biological Physics 1-11, 2013
DOI:10.1007/s10867-013-9313-0

Yuzugullu Y; Trinh CH; Fairhurst L; McPherson MJ; Pearson AR; Ogel ZB Investigating the active centre of the Scytalidium thermophilum catalase Acta Crystallographica Section F: Structural Biology and Crystallization Communications 69 369-375, 2013
DOI:10.1107/S1744309113004211

Burnett AD; Kendrick J; Russell C; Christensen J; Cunningham JE; Pearson AR; Linfield EH; Davies AG Effect of Molecular Size and Particle Shape on the Terahertz Absorption of a Homologous Series of Tetraalkylammoniunn Salts ANALYTICAL CHEMISTRY 85 7926-7934, 2013
DOI:10.1021/ac401657r

Trincao J; Christensen J; Hamilton ML; Pearson AR Dynamic structural science: Recent developments in time-resolved spectroscopy and X-ray crystallography Biochemical Society Transactions 41 1260-1264, 2013
DOI:10.1042/BST20130125

Burnett AD; Pearson AR; Russell C; Li L; Cunningham JE; Linfield EH; Davies AG; Kendrick J; Christensen J Understanding the influence of morphology on the terahertz spectra of a powdered ionic crystalline system, 2013
DOI:10.1109/IRMMW-THz.2013.6665919

Tych KM; Wood CD; Li L; Cunningham JE; Linfield EH; Davies AG; Burnett AD; Malham RW; Pearson AR; Paci E Terahertz time-domain spectroscopy of lysozyme and mouse urinary protein single crystals, 2013
DOI:10.1109/IRMMW-THz.2013.6665840

Bakker SE; Ford RJ; Barker AM; Robottom J; Saunders K; Pearson AR; Ranson NA; Stockley PG Isolation of an asymmetric RNA uncoating intermediate for a single-stranded RNA plant virus. J Mol Biol 417 65-78, 2012
DOI:10.1016/j.jmb.2012.01.017

Owen RL; Yorke BA; Pearson AR X-ray-excited optical luminescence of protein crystals: A new tool for studying radiation damage during diffraction data collection Acta Crystallographica Section D: Biological Crystallography 68 505-510, 2012
DOI:10.1107/S0907444912002946

Gumiero A; Metcalfe CL; Pearson AR; Raven EL; Moody PCE Nature of the Ferryl Heme in Compounds I and II J BIOL CHEM 286 1260-1268, 2011
DOI:10.1074/jbc.M110.183483

Smith MA; Knowles PF; McPherson MJ; Pearson AR Dissecting the mechanism of oxygen trafficking in a metalloenzyme FARADAY DISCUSS 148 269-282, 2011
DOI:10.1039/c005054g

Tych KM; Burnett AD; Wood CD; Cunningham JE; Pearson AR; Davies AG; Linfield EH Applying broadband terahertz time-domain spectroscopy to the analysis of crystalline proteins: a dehydration study J APPL CRYSTALLOGR 44 129-133, 2011
DOI:10.1107/S0021889810043372

Pearson AR; Mozzarelli A X-ray crystallography marries spectroscopy to unveil structure and function of biological macromolecules Preface BBA-PROTEINS PROTEOM 1814 731-733, 2011
DOI:10.1016/j.bbapap.2011.04.010

Owen RL; Yorke BA; Gowdy JA; Pearson AR Revealing low-dose radiation damage using single-crystal spectroscopy J SYNCHROTRON RADIAT 18 367-373, 2011
DOI:10.1107/S0909049511004250

Foster TL; Belyaeva T; Stonehouse NJ; Pearson AR; Harris M All Three Domains of the Hepatitis C Virus Nonstructural NS5A Protein Contribute to RNA Binding J VIROL 84 9267-9277, 2010
DOI:10.1128/JVI.00616-10

Foster TL; Tedbury PR; Pearson AR; Harris M A comparative analysis of the fluorescence properties of the wild-type and active site mutants of the hepatitis C virus autoprotease NS2-3 BBA-PROTEINS PROTEOM 1804 212-222, 2010
DOI:10.1016/j.bbapap.2009.10.006

Smith MA; Pirrat P; Pearson AR; Kurtis CRP; Trinh CH; Gaule TG; Knowles PF; Phillips SEV; McPherson MJ Exploring the Roles of the Metal Ions in Escherichia coli Copper Amine Oxidase BIOCHEMISTRY-US 49 1268-1280, 2010
DOI:10.1021/bi901738k

Campeotto I; Bolt AH; Harman TA; Dennis C; Trinh CH; Phillips SEV; Nelson A; Pearson AR; Berry A Structural Insights into Substrate Specificity in Variants of N-Acetylneuraminic Acid Lyase Produced by Directed Evolution J MOL BIOL 404 56-69, 2010
DOI:10.1016/j.jmb.2010.08.008

Cedervall PE; Dey M; Pearson AR; Ragsdale SW; Wilmot CM Structural Insight into Methyl-Coenzyme M Reductase Chemistry Using Coenzyme B Analogues BIOCHEMISTRY-US 49 7683-7693, 2010
DOI:10.1021/bi100458d

Owen RL; Pearson AR; Meents A; Boehler P; Thominet V; Schulze-Briese C A new on-axis multimode spectrometer for the macromolecular crystallography beamlines of the Swiss Light Source J SYNCHROTRON RADIAT 16 173-182, 2009
DOI:10.1107/S0909049508040120

Campeotto I; Carr SB; Trinh CH; Nelson AS; Berry A; Phillips SEV; Pearson AR Structure of an Escherichia coli N-acetyl-D-neuraminic acid lyase mutant, E192N, in complex with pyruvate at 1.45 angstrom resolution ACTA CRYSTALLOGR F 65 1088-1090, 2009
DOI:10.1107/S1744309109037403

Kocabas DS; Pearson AR; Phillips SEV; Bakir U; Ogel ZB; McPherson MJ; Trinh CH Crystallization and preliminary X-ray analysis of a bifunctional catalase-phenol oxidase from Scytalidium thermophilum ACTA CRYSTALLOGR F 65 486-488, 2009
DOI:10.1107/S1744309109012007

Pearson AR; Owen RL Combining X-ray crystallography and single-crystal spectroscopy to probe enzyme mechanisms BIOCHEM SOC T 37 378-381, 2009
DOI:10.1042/BST0370378

Pirrat P; Smith MA; Pearson AR; McPherson MJ; Phillips SEV Structure of a xenon derivative of Escherichia coli copper amine oxidase: confirmation of the proposed oxygen-entry pathway ACTA CRYSTALLOGR F 64 1105-1109, 2008
DOI:10.1107/S1744309108036373

Pearson AR; Pahl R; Kovaleva EG; Davidson VL; Wilmot CM Tracking X-ray derived redox changes in crystals of a methylamine dehydrogenase/amicyanin complex using single crystal UV/Vis microspectrophotometry Journal of Synchrotron Radiation 14 92-98, 2007

Pearson AR; Elmore BO; Yang C; Ferrara JD; Hooper AB; Wilmot CM The crystal structure of cytochrome P460 of Nitrosomonas europaea reveals a novel cytochrome fold and heme-protein cross-link BIOCHEMISTRY-US 46 8340-8349, 2007
DOI:10.1021/bi700086r

Johnson BJ; Cohen J; Welford RW; Pearson AR; Schulten K; Klinman JP; Wilmot CM Exploring molecular oxygen pathways in Hansenula polymorpha copper-containing amine oxidase Journal of Biological Chemistry 282 17767-17776, 2007

Pearson AR; Marimanikkuppam S; Li X; Davidson VL; Wilmot CM Isotope Labeling Studies Reveal the Order of Oxygen Incorporation into the Tryptophan Tryptophylquinone Cofactor of Methylamine Dehydrogenase Journal of the American Chemical Society 128 12416-12417, 2006
DOI:10.1021/ja064466e

Elmore BO; Pearson AR; Wilmot CM; Hooper AB Expression, purification, crystallization and preliminary X-ray diffraction of a novel Nitrosomonas europaea cytochrome, cytochrome P460 Acta Crystallographica. Section F, Structural Biology and Crystallization Communications 62 395-398, 2006
DOI:10.1107/S1744309106008785

Li X; Jones LH; Pearson AR; Wilmot CM; Davidson VL Mechanistic Possibilities in MauG-Dependent Tryptophan Tryptophylquinone Biosynthesis Biochemistry 45 13276-13283, 2006
DOI:10.1021/bi061497d

Wang Y; Li X; Jones LH; Pearson AR; Wilmot CM; Davidson VL MauG-dependent in vitro biosyntheisis of tryptophan tryptophylquinone in methylamine dehydrogenase. Journal of the American Chemical Society 127 8258-8259, 2005
DOI:10.1021/ja051734k

Jones LH; Pearson AR; Tang Y; Wilmot CM; Davidson VL Active Site Aspartate Residues Are Critical for Tryptophan Tryptophylquinone Biogenesis in Methylamine Dehydrogenase Journal of Biological Chemistry 280 17392-17396, 2005
DOI:10.1074/jbc.M500943200

Pearson AR; Mozarelli A; Rossi GL Microspectrophotometry for structural enzymology Current Opinion in Structural Biology 14 656-662, 2004

Pearson AR; De la Mora-Rey T; Graichen ME; Wang YT; Jones LH; Marimanikkupam S; Agger SA; Grimsrud PA; Davidson VL; Wilmot CM Further Insights into Quinone Cofactor Biogenesis: Probing the Role of mauG in Methylamine Dehydrogenase Tryptophan Tryptophylquinone Formation Biochemistry 43 5494-5502, 2004
DOI:10.1021/bi049863l

Pearson AR; De la Mora-Rey T; Graichen ME; Wang YT; Jones LH; Marimanikkupam S; Agger SA; Grimsrud PA; Davidson VL; Wilmot CM Further insights into quinone cofactor biogenesis: Probing the role of mauG in methylamine dehydrogenase tryptophan tryptophylquinone formation BIOCHEMISTRY-US 43 5494-5502, 2004
DOI:10.1021/bi0498631

Pearson AR; Jones LH; Higgins LA; Ashcroft AE; Wilmot CM; Davidson VL Understanding quinone cofactor biogenesis in methylamine dehydrogenase through novel cofactor generation BIOCHEMISTRY-US 42 3224-3230, 2003
DOI:10.1021/bi027073a

Wang YT; Graichen ME; Liu AM; Pearson AR; Wilmot CM; Davidson VL MauG, a Novel Diheme Protein Required for Tryptophan Tryptophylquinone Biogenesis Biochemistry 42 7318-7325, 2003
DOI:10.1021/bi034243q

Pearson AR; Wilmot CM Catching catalysis in the act: using single crystal kinetics to trap methylamine dehydrogenase reaction intermediates Biochimica et Biophysica Acta 1647 381-389, 2003

Wilmot CM; Pearson AR Cryocrystallography of metalloprotein reaction intermediates. Current Opinion in Chemical Biology 6 202-207, 2002

Muller BH; Lamoure C; le Du MH; Cattolico L; Lajeunesse E; Lemaitre F; Pearson AR; Ducancel F; Menez A; Boulain JC Improving Escherichia coli alkaline phosphatase efficacy by additional mutations inside and outside the catalytic pocket. ChemBioChem 2 517-523, 2001