Staff - School of Biomedical Sciences

Professor Alastair Hawkins
Professor of Molecular Genetics

Email: alastair.hawkins@ncl.ac.uk
Telephone: +44 (0) 191 222 7673
Fax: +44 (0) 191 222 7424
Address: Institute for Cell and Molecular Biosciences
Medical School
University of Newcastle upon Tyne
Catherine Cookson Building
Framlington Place
Newcastle upon Tyne
NE2 4HH

Publications

Nichols CE, Lamb HK, Thompson P, Omari KE, Lockyer M, Charles I, Hawkins AR, Stammers DK. Crystal structure of the dimer of two essential Salmonella typhimurium proteins, YgjD and YeaZ and calorimetric evidence for the formation of a ternary YgjD-YeaZ-YjeE complex. Protein Science 2013, (epub ahead of print).
Varsaki A, Lamb HK, Eleftheriadou O, Vandera E, Thompson P, Moncalian G, de la Cruz F, Hawkins AR, Drainas C. Interaction between relaxase MbeA and accessory protein MbeC of the conjugally mobilizable plasmid ColE1. FEBS Letters 2012, 586(6), 675-679.
Blanco B, Sedes A, Peon A, Lamb H, Hawkins AR, Castedo L, Gonzalez-Bello C. Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency. Organic & Biomolecular Chemistry 2012, 10(18), 3662-3676.
Tizón L, Otero JM, Prazeres VFV, Llamas-Saiz AL, Fox GC, van Raaij MJ, Lamb H, Hawkins AR, Ainsa JA, Castedo L, Gonzáez-Bello C. A Prodrug Approach for Improving Antituberculosis Activity of Potent Mycobacterium tuberculosis Type II Dehydroquinase Inhibitors. Journal of Medicinal Chemistry 2011, 54(17), 6063-6084.
Stamp AL, Owen P, El Omari K, Lockyer M, Lamb HK, Charles IG, Hawkins AR, Stammers DK. Crystallographic and microcalorimetric analyses reveal the structural basis for high arginine specificity in the Salmonella enterica serovar Typhimurium periplasmic binding protein STM4351. Proteins 2011, 79(7), 2352-2357.
El Omari K, Dhaliwal B, Ren J, Abrescia NGA, Lockyer M, Powell KL, Hawkins AR, Stammers DK. Structures of respiratory syncytial virus nucleocapsid protein from two crystal forms: details of potential packing interactions in the native helical form. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications 2011, 67(10), 1179-1183.
Paz S, Tizon L, Otero JM, Llamas-Saiz AL, Fox GC, van Raaij MJ, Lamb H, Hawkins AR, Lapthorn AJ, Castedo L, Gonzalez-Bello C. Tetrahydrobenzothiophene Derivatives: Conformationally Restricted Inhibitors of Type II Dehydroquinase. ChemMedChem 2011, 6(2), 266-272.
Peón A, Otero J, Tizón L, Prazeres V, Llamas-Saiz A, Fox G, Van Raaij M, Lamb H, Hawkins A, Gago F, Castedo L, González-Bello C. Understanding the key factors that control the inhibition of type II dehydroquinase by (2R)-2-benzyl-3-dehydroquinic acids. ChemMedChem 2010, 5(10), 1726-1733.
Prazeres VFV, Castedo L, Lamb H, Hawkins AR, Gonzalez-Bello C. 2-Substituted-3-Dehydroquinic Acids as Potent Competitive Inhibitors of Type II Dehydroquinase. ChemMedChem 2009, 4(12), 1980-1984.
Sanchez-Sixto C, Prazeres VFV, Castedo L, Suh SW, Lamb H, Hawkins AR, Canada FJ, Barbero JJ, Gonzalez-Bello C. Competitive inhibitors of Helicobacter pylori type II dehydroquinase: Synthesis, biological evaluation, and NMR studies. ChemMedChem 2008, 3(5), 756-770.
El Omari K, Scott K, Dhaliwal B, Ren J, Abrescia NGA, Budworth J, Lockyer M, Powell KL, Hawkins AR, Stammers DK. Crystallization and preliminary X-ray analysis of the human respiratory syncytial virus nucleocapsid protein. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications 2008, 64(11), 1019-1023.
Lamb HK, Stammers DK, Hawkins AR. Dinucleotide-sensing proteins: linking signaling networks and regulating transcription. Science Signaling 2008, 1(33), pe38.
Lamb HK, Varsaki A, Drainas C, Hawkins AR. MbeA and MbeC, proteins key to ColE1 plasmid mobilisation, interact in vitro with a 1 : 1 stoichiometry. In: FEBS Journal: Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference. 2008, Athens, Greece: Wiley-Blackwell Publishing Ltd.
Kotaka M, Johnson C, Lamb HK, Hawkins AR, Ren J, Stammers DK. Structural Analysis of the Recognition of the Negative Regulator NmrA and DNA by the Zinc Finger from the GATA-Type Transcription Factor AreA. Journal of Molecular Biology 2008, 381(2), 373-382.
Nichols CE, Lamb HK, Lockyer M, Charles IG, Pyne S, Hawkins AR, Stammers DK. Characterization of Salmonella typhimurium YegS, a putative lipid kinase homologous to eukaryotic sphingosine and diacylglycerol kinases. Proteins: Structure, Function and Genetics 2007, 68(1), 13-25.
Lamb HK, Thompson P, Elliott C, Charles IG, Richards J, Lockyer M, Watkins N, Nichols C, Stammers DK, Bagshaw CR, Cooper A, Hawkins AR. Functional analysis of the GTPases EngA and YhbZ encoded by Salmonella typhimurium. Protein Science 2007, 16(11), 2391-2402.
Nichols CE, Johnson C, Lamb HK, Lockyer M, Charles IG, Hawkins AR, Stammers DK. Structure of the ribosomal interacting GTPase YjeQ from the enterobacterial species Salmonella typhimurium. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 2007, 63(11), 922-928.
Prazeres VFV, Sanchez-Sixto C, Castedo L, Canales A, Canada FJ, Jimenez-Barbero J, Lamb H, Hawkins AR, Gonzalez-Bello C. Determination of the bound conformation of a competitive nanomolar inhibitor of Mycobacterium tuberculosis type II dehydroquinase by NMR spectroscopy. ChemMedChem 2006, 1(9), 990-996.
Nichols CE, Johnson C, Lockyer M, Charles IG, Lamb HK, Hawkins AR, Stammers DK. Structural characterization of Salmonella typhimurium YeaZ, an M22 O-sialoglycoprotein endopeptidase homolog. Proteins: Structure, Function and Genetics 2006, 64(1), 111-123.
Dhaliwal B, Ren J, Lockyer M, Charles I, Hawkins AR, Stammers DK. Structure of Staphylococcus aureus cytidine monophosphate kinase in complex with cytidine 5′-monophosphate. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 2006, 62(8), 710-715.
El Omari K, Dhaliwal B, Hawkins A, Lockyer M, Charles I, Stammers DK. Structure of Staphylococcus aureus guanylate monophosphate kinase. Acta Crystallographica F 2006, 62(10), 949-953.
El Omari K, Dhaliwal B, Lockyer M, Charles I, Hawkins AR, Stammers DK. Structure of Staphylococcus aureus guanylate monophosphate kinase. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 2006, 62(10), 949-953.
Kotaka M, Dhaliwal B, Ren J, Nichols CE, Angell R, Lockyer M, Hawkins AR, Stammers DK. Structures of S. aureus thymidylate kinase reveal an atypical active site configuration and an intermediate conformational state upon substrate binding. Protein Science 2006, 15(4), 774-784.
Kotaka M, Ren J, Lockyer M, Hawkins AR, Stammers DK. Structures of R- and T-state Escherichia coli aspartokinase III: Mechanisms of the allosteric transition and inhibition by lysine. Journal of Biological Chemistry 2006, 281(42), 31544-31552.
Lamb HK, Mee C, Xu W, Liu L, Blond S, Cooper A, Charles IG, Hawkins AR. The affinity of a major Ca2+ binding site on GRP78 is differentially enhanced by ADP and ATP. Journal of Biological Chemistry 2006, 281(13), 8796-8805.
Ren J, Kotaka M, Lockyer M, Lamb HK, Hawkins AR, Stammers DK. GTP cyclohydrolase II structure and mechanism. Journal of Biological Chemistry 2005, 280(44), 36912-36919.
Sanchez-Sixto C, Prazeres VFV, Castedo L, Lamb H, Hawkins AR, Gonzalez-Bello C. Structure-based design, synthesis, and biological evaluation of inhibitors of Mycobacterium tuberculosis type II dehydroquinase. Journal of Medicinal Chemistry 2005, 48(15), 4871-4881.
Park A, Lamb HK, Nichols C, Moore JD, Brown KA, Cooper A, Charles IG, Stammers DK, Hawkins AR. Biophysical and kinetic analysis of wild-type and site-directed mutants of the isolated and native dehydroquinate synthase domain of the AROM protein. Protein Science 2004, 13(8), 2108-2119.
Nichols CE, Ren J, Leslie K, Dhaliwal B, Lockyer M, Charles I, Hawkins AR, Stammers DK. Comparison of ligand-induced conformational changes and domain closure mechanisms, between prokaryotic and eukaryotic dehydroquinate synthases. Journal of Molecular Biology 2004, 343(3), 533-546.
Nichols CE, Lockyer M, Hawkins AR, Stammers DK. Crystal structures of Staphylococcus aureus type I dehydroquinase from enzyme turnover experiments. Proteins: Structure, Function and Genetics 2004, 56(3), 625-628.
Dhaliwal B, Nichols CE, Ren J, Lockyer M, Charles I, Hawkins AR, Stammers DK. Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. FEBS Letters 2004, 574(1-3), 49-54.
Nichols CE, Dhaliwal B, Lockyer M, Hawkins AR, Stammers DK. High-resolution structures reveal details of domain closure and "half-of-sites-reactivity" in Escherichia coli aspartate β-semialdehyde dehydrogenase. Journal of Molecular Biology 2004, 341(3), 797-806.
Lamb HK, Ren J, Park A, Johnson C, Leslie K, Cocklin S, Thompson P, Mee C, Cooper A, Stammers DK, Hawkins AR. Modulation of the ligand binding properties of the transcription repressor NmrA by GATA-containing DNA and site-directed mutagenesis. Protein Science 2004, 13(12), 3127-3138.
Nichols CE, Hawkins AR, Stammers DK. Structure of the 'open' form of Aspergillus nidulans 3-dehydroquinate synthase at 1.7 Å resolution from crystals grown following enzyme turnover. Acta Crystallographica Section D: Biological Crystallography 2004, 60(5), 971-973.
Nichols CE, Ren J, Lamb HK, Hawkins AR, Stammers DK. Ligand-induced conformational changes and a mechanism for domain closure in Aspergillus nidulans dehydroquinate synthase. Journal of Molecular Biology 2003, 327(1), 129-144.
Lamb HK, Leslie K, Dodds AL, Nutley M, Cooper A, Johnson C, Thompson P, Stammers DK, Hawkins AR. The negative transcriptional regulator NmrA discriminates between oxidized and reduced dinucleotides. Journal of Biological Chemistry 2003, 278(34), 32107-32114.
Brown KA, Carpenter EP, Watson KA, Coggins JR, Hawkins AR, Koch MHJ, Svergun DI. Twists and turns: A tale of two shikimate-pathway enzymes. Biochemical Society Transactions 2003, 31(3), 543-547.
Tewari YB, Hawkins AR, Lamb HK, Goldberg RN. A thermodynamic study of the reactions: {2-dehydro-3-deoxy-D-arabino-heptanoate 7-phosphate(aq) = 3-dehydroquinate(aq) + phosphate(aq)} and {3-dehydroquinate(aq) = 3-dehydroshikimate(aq) + H2O(1)}. Journal of Chemical Thermodynamics 2002, 34(10), 1671-1691.
Lee WH, Perles LA, Nagem RAP, Shrive AK, Hawkins A, Sawyer L, Polikarpov I. Comparison of different crystal forms of 3-dehydroquinase from Salmonella typhi and its implication for the enzyme activity. Acta Crystallographica Section D: Biological Crystallography 2002, 58(part 5), 798-804.
Bird LE, Ren JS, Zhang JC, Foxwell N, Hawkins AR, Charles IG, Stammers DK. Crystal structure of SANOS, a bacterial nitric oxide synthase oxygenase protein from Staphylococcus aureus. Structure 2002, 10(12), 1687-1696.
Watts C, Si-Hoe SM, Lamb HK, Levett LJ, Coggins JR, Hawkins AR. Kinetic analysis of the interaction between the QutA and QutR transcription-regulating proteins. Proteins: Structure, Function and Genetics 2002, 48(2), 161-168.
Spiers A, Lamb HK, Cocklin S, Wheeler KA, Budworth J, Dodds AL, Pallen MJ, Maskell DJ, Charles IG, Hawkins AR. PDZ domains facilitate binding of high temperature requirement protease A (HtrA) and tail-specific protease (Tsp) to heterologous substrates through recognition of the small stable RNA A (ssrA)-encoded peptide. Journal of Biological Chemistry 2002, 277(42), 39443-39449.
Nichols CE, Cocklin S, Dodds A, Ren J, Lamb H, Hawkins AR, Stammers DK. Expression, purification and crystallization of Aspergillus nidulans NmrA, a negative regulatory protein involved in nitrogen-metabolite repression. Acta Crystallographica Section D: Biological Crystallography 2001, 57(11), 1722-1725.
Nichols CE, Ren J, Lamb H, Haldane F, Hawkins AR, Stammers DK. Identification of many crystal forms of Aspergillus nidulans dehydroquinate synthase. Acta Crystallographica Section D: Biological Crystallography 2001, 57(2), 306-309.
Stammers DK, Ren J, Leslie K, Nichols CE, Lamb HK, Cocklin S, Dodds A, Hawkins AR. The structure of the negative transcriptional regulator NmrA reveals a structural superfamily which includes the short-chain dehydrogenase/reductases. EMBO Journal 2001, 20(23), 6619-6626.
Levett LJ, Si-Hoe SM, Liddle S, Wheeler K, Smith D, Lamb HK, Newton GH, Coggins JR, Hawkins AR. Identification of domains responsible for signal recognition and transduction within the QUTR transcription repressor protein. Biochemical Journal 2000, 350(1), 189-197.
Parker EJ, Bello CG, Coggins JR, Hawkins AR, Abell C. Mechanistic studies on type I and type II dehydroquinase with (6R)- and (6S)-6-fluoro-3-dehydroquinic acids. Bioorganic and Medicinal Chemistry Letters 2000, 10(3), 231-234.
Frederickson M, Parker EJ, Hawkins AR, Coggins JR, Abell C. Selective inhibition of type II dehydroquinases. Journal of Organic Chemistry 1999, 64(8), 2612-2613.
Gonzalez-Bello C, Coggins TJR, Hawkins AR, Abell C. Synthesis of 4-deoxyquinic, 4-deoxyshikimic and 4-deoxy-3-dehydroshikimic acids. Journal of the Chemical Society - Perkin Transactions 1 1999, (8), 849-854.
Price NC, Boam DJ, Kelly SM, Duncan D, Krell T, Gourley DG, Coggins JR, Virden R, Hawkins AR. The folding and assembly of the dodecameric type II dehydroquinases. Biochemical Journal 1999, 338(1), 195-202.
Price NC, Boam DJ, Kelly SM, Duncan D, Krell T, Gourley DG, Coggins JR, Virden R, Hawkins AR. The folding and assembly of the dodecameric type II dehydroquinases. Biochemical Journal 1999, 338, 195-202.
Gourley DG, Shrive AK, Polikarpov I, Krell T, Coggins JR, Hawkins AR, Isaacs NW, Sawyer L. The two types of 3-dehydroquinase have distinct structures but catalyze the same overall reaction. Nature Structural Biology 1999, 6(6), 521-525.

Newcastle University

School of Biomedical Sciences

Professor Alastair Hawkins Professor of Molecular Genetics

Professor Alastair Hawkins
Professor of Molecular Genetics