People

Dr Jonathan Worrall

Senior Lecturer
School of Life Sciences
Dr Jonathan Worrall

Profile

Biography

2007-present: University of Essex, UK 2005-2007: Post-doctoral research associate, Department of Biochemistry, University of Cambridge, UK 1999-2005: Post-doctoral research associate, Leiden Institute of Chemistry, Leiden University, The Netherlands 1995-1999: PhD in Bioinorganic Chemistry, Department of Chemistry, Newcastle University, UK (Supervisor Professor A.G. Sykes FRS) 1992-1995: BSc (Hons) Medicinal Chemistry, Newcastle University, UK Local Ambassador for the Biochemical Society Secretary of the Inorganic Biochemistry Discussion Group, an interest group of the Royal Society of Chemistry Current group members Mr Oliver Deacon Miss Megan Straw Former group members Dr Amanda Chaplin (PhD, graduated 2016) Dr Andreas Ioannis Karsisiotis(Post-doc) Dr Tatiana Porto (PhD, graduated 2016) Dr Katie Blundell (PhD, graduated 2014) Dr Badri Rajagopal (PhD, graduated 2013) Benedict Tan (MSc, graduated 2013) Srivatsa Dwarakanath (MRes, graduated 2012) Emily Colley (Wellcome Trust Biomedical summer student 2013) Emma Blundell (Society of Biology summer student 2012)

Research and professional activities

Research interests

Microbial Biotechnology

Copper homeostasis in Streptomyces

Lipid induced apoptosis

Structural Biochemistry

Current research

My research focus is on the role of metal ions and metalloproteins in biology.

Copper and StreptomycesWe are interested in the role of copper on the morphological development of the antibiotic producing actinobacterium Streptomyces lividans. Using microbial genetics, structural biology, spectroscopy and RNA-seq analysis we have identified and characterised copper sensing and trafficking pathways leading to the metallation of cuproenzymes that are critical for initiating development in this industrially important microbe.

Mitochondrial cytochrome c and apoptosisThe haem containing redox protein cytochrome c is a key mitochondrial protein that plays an important role in the life and death decisions of a cell. In the mitochondrial apoptosis pathway cytochrome c is released from the mitochondria into the cytosol leading to the formation of the apoptosome assembly, a cellular platform to initiate caspase activity triggering cell death. The selective oxidation by cytochorme c of a unique inner-membrane mitochondrial phospholipid, diphosphatidylglycerol, better known as cardiolipin has been demonstrated to trigger events that lead to cytochrome c release from the mitochondria. Using NMR and EPR spectroscopies we are investigating the interaction and complex formed bewteen cytochorme c and cardiolipin.

Teaching and supervision

Current teaching responsibilities

  • Quantitative methods for Life Sciences (BS141)

  • Enterprise and Employability for the Biosciences (BS211)

  • Metals in Biology (BS228)

  • Proteins and Macromolecular Assemblies (BS230)

  • Enterprise and Employability for the Biosciences (Assessed in Following Year) (BS411)

  • Research Project in Biomolecular Science (BS831)

Previous supervision

Megan Laura Straw
Megan Laura Straw
Thesis title: Storing Copper in Streptomyces Lividans: Structural and Biochemical Properties of a Copper Storage Protein
Degree subject: Biological Sciences
Degree type: Doctor of Philosophy
Awarded date: 5/7/2019
Oliver Mario Deacon
Oliver Mario Deacon
Thesis title: Structural Dynamics and Spectroscopic Studies of Human Cytochrome C: Linking Dynamics and Disease
Degree subject: Biochemistry
Degree type: Doctor of Philosophy
Awarded date: 25/6/2018
Amanda Kay Chaplin
Amanda Kay Chaplin
Thesis title: Metalloenzymes Required for Glycan Processing and Morphological Development in Streptomyces Lividans
Degree subject: Biochemistry
Degree type: Doctor of Philosophy
Awarded date: 23/3/2016
Tatiana De Vasconcelos Porto
Tatiana De Vasconcelos Porto
Thesis title: Structural and Kinetic Studies of a Copper Sensor Protein in Streptomyces Lividans
Degree subject: Biochemistry
Degree type: Doctor of Philosophy
Awarded date: 21/3/2016
Katie Laura Irene May Blundell
Katie Laura Irene May Blundell
Thesis title: Copper Trafficking in Streptomyces Lividans: Structural and Biochemical Characterisation of Two Copper Chaperones
Degree subject: Biochemistry
Degree type: Doctor of Philosophy
Awarded date: 8/5/2014
Badri Sreenivasachar Rajagopal
Badri Sreenivasachar Rajagopal
Thesis title: Interactions of Mitochondrial Cytochrome C with Phospholipids
Degree subject: Biochemistry
Degree type: Doctor of Philosophy
Awarded date: 12/2/2013

Publications

Journal articles (58)

Chaplin, AK., Chicano, TM., Hampshire, BV., Wilson, MT., Hough, MA., Svistunenko, DA. and Worrall, JAR., (2019). An Aromatic Dyad Motif in Dye Decolourising Peroxidases Has Implications for Free Radical Formation and Catalysis. Chemistry – A European Journal. 25 (24), 6141-6153

Straw, ML., Hough, MA., Wilson, MT. and Worrall, JAR., (2019). A histidine residue and a tetranuclear cuprous‐thiolate cluster dominate the copper loading landscape of a copper storage protein from Streptomyces lividans. Chemistry – A European Journal. 25 (45), 10678-10688

Ebrahim, A., Moreno-Chicano, T., Appleby, MV., Chaplin, AK., Beale, JH., Sherrell, DA., Duyvesteyn, HME., Owada, S., Tono, K., Sugimoto, H., Strange, RW., Worrall, JAR., Axford, D., Owen, RL. and Hough, MA., (2019). Dose-resolved serial synchrotron and XFEL structures of radiation-sensitive metalloproteins. IUCrJ. 6 (4), 543-551

Deacon, OM., Svistunenko, DA., Moore, GR., Wilson, MT. and Worrall, JAR., (2018). Naturally Occurring Disease-Related Mutations in the 40–57 Ω-Loop of Human Cytochrome c Control Triggering of the Alkaline Isomerization. Biochemistry. 57 (29), 4276-4288

Straw, ML., Chaplin, AK., Hough, MA., Paps, J., Bavro, VN., Wilson, MT., Vijgenboom, E. and Worrall, JAR., (2018). A cytosolic copper storage protein provides a second level of copper tolerance in Streptomyces lividans.. Metallomics: integrated biometal science. 2018 (10), 180-193

Karsisiotis, AI., Deacon, OM., Macdonald, C., Blumenschein, TMA., Moore, GR. and Worrall, JAR., (2017). Near-complete backbone resonance assignments of acid-denatured human cytochrome c in dimethylsulfoxide: a prelude to studying interactions with phospholipids. Biomolecular NMR Assignments. 11 (2), 165-168

Chaplin, AK., Wilson, MT. and Worrall, JAR., (2017). Kinetic characterisation of a dye decolourising peroxidase from Streptomyces lividans: New insight into the mechanism of anthraquinone dye decolourisation. Dalton Transactions. 46 (29), 9420-9429

Chaplin, AK., Bernini, C., Sinicropi, A., Basosi, R., Worrall, JAR. and Svistunenko, DA., (2017). Tyrosine or Tryptophan? Modifying a Metalloradical Catalytic Site by Removal of the Cys–Tyr Cross‐Link in the Galactose 6‐Oxidase Homologue GlxA. Angewandte Chemie International Edition. 129 (23), 6602-6606

Kekilli, D., Moreno-Chicano, T., Chaplin, AK., Horrell, S., Dworkowski, FSN., Worrall, JAR., Strange, RW. and Hough, MA., (2017). Photoreduction and validation of haem?ligand intermediate states in protein crystals by in situ single-crystal spectroscopy and diffraction. IUCrJ. 4 (3), 263-270

Deacon, OM., Karsisiotis, AI., Moreno-Chicano, T., Hough, MA., Macdonald, C., Blumenschein, TMA., Wilson, MT., Moore, GR. and Worrall, JAR., (2017). Heightened Dynamics of the Oxidized Y48H Variant of Human Cytochrome c Increases Its Peroxidatic Activity.. Biochemistry. 56 (46), 6111-6124

Chaplin, AK., Svistunenko, DA., Hough, MA., Wilson, MT., Vijgenboom, E. and Worrall, JAR., (2017). Active site maturation and activity of the copper-radical oxidase GlxA is governed by a tryptophan residue. The Biochemical Journal. 474 (5), 809-825

Chaplin, AK., Wilson, MT., Hough, MA., Svistunenko, DA., Hemsworth, GR., Walton, PH., Vijgenboom, E. and Worrall, JAR., (2016). Heterogeneity in the Histidine-brace Copper Coordination Sphere in Auxiliary Activity Family 10 (AA10) Lytic Polysaccharide Monooxygenases. Journal of Biological Chemistry. 291 (24), 12838-12850

Petrus, MLC., Vijgenboom, E., Chaplin, AK., Worrall, JAR., van Wezel, GP. and Claessen, D., (2016). The DyP-type peroxidase DtpA is a Tat-substrate required for GlxA maturation and morphogenesis in Streptomyces. Open Biology. 6 (1), 150149-150149

Karsisiotis, AI., Deacon, OM., Wilson, MT., Macdonald, C., Blumenschein, TMA., Moore, GR. and Worrall, JAR., (2016). Increased dynamics in the 40–57 Ω-loop of the G41S variant of human cytochrome c promote its pro-apoptotic conformation. Scientific Reports. 6 (1), 30447-

Chaplin, AK., Tan, BG., Vijgenboom, E. and Worrall, JAR., (2015). Copper trafficking in the CsoR regulon of Streptomyces lividans. Metallomics. 7 (1), 145-155

Chaplin, AK., Petrus, MLC., Mangiameli, G., Hough, MA., Svistunenko, DA., Nicholls, P., Claessen, D., Vijgenboom, E. and Worrall, JAR., (2015). GlxA is a new structural member of the radical copper oxidase family and is required for glycan deposition at hyphal tips and morphogenesis ofStreptomyces lividans. Biochemical Journal. 469 (3), 433-444

Karsisiotis, AI., Deacon, OM., Rajagopal, BS., Macdonald, C., Blumenschein, TMA., Moore, GR. and Worrall, JAR., (2015). Backbone resonance assignments of ferric human cytochrome c and the pro-apoptotic G41S mutant in the ferric and ferrous states. Biomolecular NMR Assignments. 9 (2), 415-419

Porto, TV., Wilson, MT. and Worrall, JAR., (2015). Copper and nickel bind via two distinct kinetic mechanisms to a CsoR metalloregulator. Dalton Transactions. 44 (46), 20176-20185

Porto, TV., Hough, MA. and Worrall, JAR., (2015). Structural insights into conformational switching in the copper metalloregulator CsoR fromStreptomyces lividans. Acta Crystallographica Section D Biological Crystallography. 71 (9), 1872-1878

Tan, BG., Vijgenboom, E. and Worrall, JAR., (2014). Conformational and thermodynamic hallmarks of DNA operator site specificity in the copper sensitive operon repressor from Streptomyces lividans. Nucleic Acids Research. 42 (2), 1326-1340

Blundell, KLIM., Hough, MA., Vijgenboom, E. and Worrall, JAR., (2014). Structural and mechanistic insights into an extracytoplasmic copper trafficking pathway inStreptomyces lividans. Biochemical Journal. 459 (3), 525-538

Hough, MA., Silkstone, G., Worrall, JAR. and Wilson, MT., (2014). NO Binding to the Proapoptotic Cytochrome c–Cardiolipin Complex. NITRIC OXIDE. 96, 193-209

Blundell, KLIM., Wilson, MT., Vijgenboom, E. and Worrall, JAR., (2013). The role of the Cys-X-X-X-Cys motif on the kinetics of cupric ion loading to the Streptomyces lividans Sco protein. Dalton Transactions. 42 (29), 10608-10608

Blundell, KLIM., Wilson, MT., Svistunenko, DA., Vijgenboom, E. and Worrall, JAR., (2013). Morphological development and cytochrome c oxidase activity in Streptomyces lividans are dependent on the action of a copper bound Sco protein. Open Biology. 3 (1), 120163-120163

Rajagopal, BS., Edzuma, AN., Hough, MA., Blundell, KLIM., Kagan, VE., Kapralov, AA., Fraser, LA., Butt, JN., Silkstone, GG., Wilson, MT., Svistunenko, DA. and Worrall, JAR., (2013). The hydrogen-peroxide-induced radical behaviour in human cytochromec–phospholipid complexes: implications for the enhanced pro-apoptotic activity of the G41S mutant. Biochemical Journal. 456 (3), 441-452

Rajagopal, BS., Silkstone, GG., Nicholls, P., Wilson, MT. and Worrall, JAR., (2012). An investigation into a cardiolipin acyl chain insertion site in cytochrome c. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1817 (5), 780-791

Mason, JM., Bendall, DS., Howe, CJ. and Worrall, JAR., (2012). The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c6A. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1824 (2), 311-318

Svistunenko, DA., Worrall, JAR., Chugh, SB., Haigh, SC., Ghiladi, RA. and Nicholls, P., (2012). Ferric haem forms of Mycobacterium tuberculosis catalase-peroxidase probed by EPR spectroscopy: Their stability and interplay with pH. Biochimie. 94 (6), 1274-1280

Dwarakanath, S., Chaplin, AK., Hough, MA., Rigali, S., Vijgenboom, E. and Worrall, JAR., (2012). Response to Copper Stress inStreptomyces lividansExtends beyond Genes under Direct Control of a Copper-sensitive Operon Repressor Protein (CsoR). Journal of Biological Chemistry. 287 (21), 17833-17847

Rajagopal, BS., Wilson, MT., Bendall, DS., Howe, CJ. and Worrall, JAR., (2011). Structural and kinetic studies of imidazole binding to two members of the cytochrome c 6 family reveal an important role for a conserved heme pocket residue. JBIC Journal of Biological Inorganic Chemistry. 16 (4), 577-588

Worrall, JAR. and Mason, JM., (2011). Thermodynamic analysis of Jun-Fos coiled coil peptide antagonists. FEBS Journal. 278 (4), 663-672

Volkov, AN., Nicholls, P. and Worrall, JAR., (2011). The complex of cytochrome c and cytochrome c peroxidase: The end of the road?. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1807 (11), 1482-1503

Bischin, C., Deac, F., Silaghi-Dumitrescu, R., Worrall, JAR., Rajagopal, BS., Damian, G. and Cooper, CE., (2011). Ascorbate peroxidase activity of cytochromec. Free Radical Research. 45 (4), 439-444

Worrall, JAR. and Vijgenboom, E., (2010). Copper mining in Streptomyces: enzymes, natural products and development. Natural Product Reports. 27 (5), 742-742

Volkov, AN., Bashir, Q., Worrall, JAR., Ullmann, GM. and Ubbink, M., (2010). Shifting the Equilibrium between the Encounter State and the Specific Form of a Protein Complex by Interfacial Point Mutations. Journal of the American Chemical Society. 132 (33), 11487-11495

Volkov, AN., Bashir, Q., Worrall, JAR. and Ubbink, M., (2009). Binding Hot Spot in the Weak Protein Complex of Physiological Redox Partners Yeast Cytochrome c and Cytochrome c Peroxidase. Journal of Molecular Biology. 385 (3), 1003-1013

Worrall, JAR., Luisi, BF., Schlarb-Ridley, BG., Bendall, DS. and Howe, CJ., (2008). Cytochromec6A: discovery, structure and properties responsible for its low haem redox potential. Biochemical Society Transactions. 36 (6), 1175-1179

Worrall, JAR., Howe, FS., McKay, AR., Robinson, CV. and Luisi, BF., (2008). Allosteric Activation of the ATPase Activity of theEscherichia coliRhlB RNA Helicase. Journal of Biological Chemistry. 283 (9), 5567-5576

Worrall, JAR., Górna, M., Crump, NT., Phillips, LG., Tuck, AC., Price, AJ., Bavro, VN. and Luisi, BF., (2008). Reconstitution and Analysis of the Multienzyme Escherichia coli RNA Degradosome. Journal of Molecular Biology. 382 (4), 870-883

Worrall, JAR., Schlarb-Ridley, BG., Reda, T., Marcaida, MJ., Moorlen, RJ., Wastl, J., Hirst, J., Bendall, DS., Luisi, BF. and Howe, CJ., (2007). Modulation of Heme Redox Potential in the Cytochromec6Family. Journal of the American Chemical Society. 129 (30), 9468-9475

Worrall, JAR., Górna, M., Pei, XY., Spring, DR., Nicholson, RL. and Luisi, BF., (2007). Design and chance in the self-assembly of macromolecules. Biochemical Society Transactions. 35 (3), 502-507

Worrall, JAR. and Luisi, BF., (2007). Information available at cut rates: structure and mechanism of ribonucleases. Current Opinion in Structural Biology. 17 (1), 128-137

Volkov, AN., Worrall, JAR., Holtzmann, E. and Ubbink, M., (2006). Solution structure and dynamics of the complex between cytochrome c and cytochrome c peroxidase determined by paramagnetic NMR. Proceedings of the National Academy of Sciences. 103 (50), 18945-18950

Worrall, JAR., Machczynski, MC., Keijser, BJF., di Rocco, G., Ceola, S., Ubbink, M., Vijgenboom, E. and Canters, GW., (2006). Spectroscopic Characterization of a High-Potential Lipo-Cupredoxin Found inStreptomycescoelicolor. Journal of the American Chemical Society. 128 (45), 14579-14589

Marcaida, MJ., Schlarb-Ridley, BG., Worrall, JAR., Wastl, J., Evans, TJ., Bendall, DS., Luisi, BF. and Howe, CJ., (2006). Structure of Cytochrome c6A, a Novel Dithio-cytochrome of Arabidopsis thaliana, and its Reactivity with Plastocyanin: Implications for Function. Journal of Molecular Biology. 360 (5), 968-977

(2006). CORRECTION. Protein Science. 15 (6), 1563-1563

Volkov, AN., Ferrari, D., Worrall, JAR., Bonvin, AMJJ. and Ubbink, M., (2006). The orientations of cytochrome c in the highly dynamic complex with cytochrome b(5) visualized by NMR and docking using HADDOCK (vol 14, pg 799, 2005). PROTEIN SCIENCE. 15 (6), 1563-1563

Volkov, AN., Ferrari, D., Worrall, JAR., Bonvin, AMJJ. and Ubbink, M., (2005). The orientations of cytochromecin the highly dynamic complex with cytochromeb5visualized by NMR and docking using HADDOCK. Protein Science. 14 (3), 799-811

Worrall, JAR., Van Roon, A-MM., Ubbink, M. and Canters, GW., (2005). The effect of replacing the axial methionine ligand with a lysine residue in cytochrome c-550 from Paracoccus versutus assessed by X-ray crystallography and unfolding. FEBS Journal. 272 (10), 2441-2455

Worrall, JAR., Diederix, REM., Prudêncio, M., Lowe, CE., Ciofi-Baffoni, S., Ubbink, M. and Canters, GW., (2005). The Effects of Ligand Exchange and Mobility on the Peroxidase Activity of a Bacterial Cytochrome c upon Unfolding. ChemBioChem. 6 (4), 747-758

Diederix, REM., Fittipaldi, M., Worrall, JAR., Huber, M., Ubbink, M. and Canters, GW., (2003). Kinetic Stability of the Peroxidase Activity of Unfolded Cytochromec:  Heme Degradation and Catalyst Inactivation by Hydrogen Peroxide. Inorganic Chemistry. 42 (22), 7249-7257

Worrall, JAR., Reinle, W., Bernhardt, R. and Ubbink, M., (2003). Transient Protein Interactions Studied by NMR Spectroscopy:  The Case of Cytochromecand Adrenodoxin†. Biochemistry. 42 (23), 7068-7076

Worrall, JAR., Liu, Y., Crowley, PB., Nocek, JM., Hoffman, BM. and Ubbink, M., (2002). Myoglobin and Cytochromeb5:  A Nuclear Magnetic Resonance Study of a Highly Dynamic Protein Complex†. Biochemistry. 41 (39), 11721-11730

Crowley, PB., Rabe, KS., Worrall, JAR., Canters, GW. and Ubbink, M., (2002). The ternary complex of cytochrome f and cytochrome c: Identification of a second binding site and competition for plastocyanin binding. ChemBioChem. 3 (6), 526-533

Ubbink, M., Worrall, JAR., Canters, GW., Groenen, EJJ. and Huber, M., (2002). Paramagnetic Resonance of Biological Metal Centers. Annual Review of Biophysics and Biomolecular Structure. 31 (1), 393-422

Crowley, PB., Rabe, KS., Worrall, JAR., Canters, GW. and Ubbink, M., (2002). The Ternary Complex of Cytochrome f and Cytochrome c: Identification of a Second Binding Site and Competition for Plastocyanin Binding. ChemBioChem. 3 (6), 526-526

Worrall, JAR., Kolczak, U., Canters, GW. and Ubbink, M., (2001). Interaction of Yeast Iso-1-cytochromecwith CytochromecPeroxidase Investigated by [15N,1H] Heteronuclear NMR Spectroscopy†. Biochemistry. 40 (24), 7069-7076

Im, S-C., Worrall, JAR., Liu, G., Aliverti, A., Zanetti, G., Luchinat, C., Bertini, I. and Sykes, AG., (2000). The CrIIL Reduction of [2Fe-2S] Ferredoxins and Site of Attachment of CrIIIUsing1H NMR and Site-Directed Mutagenesis. Inorganic Chemistry. 39 (8), 1755-1764

Conferences (3)

Karsisiotis, AI., Deacon, OM., Wilson, MT., Macdonald, C., Blumenschein, TMA., Moore, GR. and Worrall, JAR., (2017). The G41S Variant of Human Cytochrome C Enhances Apoptosis via Increased Dynamics

Worrall, JAR., Volkov, A., Canters, GW. and Ubbink, M., (2001). Heme protein-protein interactions studied by NMR

Ubbink, M., Crowley, PB. and Worrall, JAR., (2001). Dynamics of electron transfer protein complexes probed by NMR

Grants and funding

2019

Protein Detection Kit

East Suffolk and North Essex NHS Foundation Trust

2018

High hit-rate, high-throughput serial protein crystallography at SACLA using fixed target silicon nitride chips

Biotechnology and Biological Sciences Research Council

2017

The role of carbohydrate binding modules appended to lytic polysaccharide monooxygenases on substrate binding

Biochemical Society

The role of carbohydrate binding modules appended to lytic polysaccharide monooxygenases on substrate binding

Biochemical Society

Creating new starch active copper LPMOs through the generation of loop libraries

Biotechnology and Biological Sciences Research Council

2013

Characterisation of a protein bound free radical induced by hydrogen peroxide

Wellcome Trust

Fat(al) attraction of cytochrome c: A new approach to study protein-lipid interaction

Leverhulme Trust

2012

Elucidating the maturation pathway of a cuproenzyme proposed to be critical for motphological development in Steptomyces lividans

Society of Biology

2011

Summer Vacation Studentship - Amanda Chaplin

Biochemical Society

2008

Protein Interactions Between A Dead-Box

The Royal Society

Contact

jworrall@essex.ac.uk
+44 (0) 1206 872095

Location:

3SW.5.23, Colchester Campus