B.A. (Cantab.) 1967,
Natural & Electrical Sciences
A.M.I.E.E. 1967 - Now MIET
M.A. (Cantab.) 1971
Ph.D (London) 1974, Physics
D.C.C. (Chelsea, London) 1976, Biochemistry
Sc.D. (Cantab.) 1986, Biology
C. Chem., M.R.S.C. 1993; F.R.S.C. (Fellow of the Royal Society of
Chemistry) 1998
Biological Chemistry
Department, John Innes Centre, Colney, Norwich NR4 7UH, UK
Telephone:
+(44)-(0)1603-450742
Fax:
+(44)-(0)1603-450018
Email: david.lowe@bbsrc.ac.uk
Latest Update: 25th April 2007
Biological
Chemistry Department Home Page
Computational and Systems Biology Department Home Page
I use a variety of techniques to study the structure and function of a number of metalloproteins at the molecular and atomic levels. This is often done in collaboration with other scientists from within the John Innes Centre, from other partners in the Norwich Research Park, or from various institutions worldwide. I also manage the Computational and Systems Biology Department at JIC. I am a member, and was the previous Chairman, of the Electron Spin Resonance Group of the Royal Society of Chemistry, a member and previous Treasurer of the Inorganic Biochemistry Discussion Group of the Royal Society of Chemistry and am a member and past Chairman of the Management Panel for the EPSRC National EPR Service. I coordinated an EU RTN network on the functioning of xanthine oxidase family enzymes.
The
principal in house methods I use are steady-state and pre-steady-state
enzyme kinetics and modeling, together with the magnetic techniques of
electron paramagnetic resonance (epr or esr) and electron nuclear double
resonance (ENDOR).
The main enzymes I study are nitrogenase, xanthine oxidase family enzymes, and nitrate reductase plus a number of other molybdenum-containing enzymes. I also work on other proteins with paramagnetic centres including flavins, copper, haems and iron-sulfur centres.
Nitrogenase is responsible for the biological fixation of
nitrogen gas, a process by which this dinitrogen is reduced to ammonia.
All organisms require fixed nitrogen for growth because it is an essential
component of nucleic acids and proteins. However only a small number of
microorganisms contain nitrogenase and are therefore capable of catalyzing
this process. Industrially, large quantities of fossil fuels are used in
capital intensive plants to fix nitrogen gas, largely for agricultural use
as fertilizer. It is important to know how the enzyme works because: we
ought to understand this processes which is crucial for life; because only
if we fully understand it can we learn how to manipulate it with the aim
of improving agricultural efficiency; and because it uses unknown
chemistry to catalyze the reaction, a knowledge of which could lead to the
development of new catalysts.
Xanthine Oxidase is the most thoroughly studied of the enzymes
containing the molybdenum cofactor, a group that includes enzymes that
catalyze the oxidative hydroxylation of a range of heterocyclic compounds
and aldehydes as well as oxygen atom transfer to or from small molecules
and ions such as nitrate. We are well on the way to understanding the fine
detail of the way in which this enzyme works.
Nitrate Reductases catalyze the reduction of nitrate to nitrite
and fall into two main categories, both of which contain molybdenum at the
nitrate reducing active site. Assimilatory nitrate reductases are
responsible for the initial reaction in the uptake of nitrate into
organisms; in higher plants this is the rate-limiting, controlled step
which often limits the overall growth rate of agricultural crops and we
are studying how 14-3-3 proteins control the enzyme's activity. The
dissimilatory enzymes are terminal electron acceptors in a number of
microorganisms, usually in oxygen-deficient environments such as
waterlogged soils, and are the initial step in the process of
denitrification; this can lead to loss of fixed nitrogen from the soil and
to the production of greenhouse gases.
Evidence for a dynamic role for homocitrate during nitrogen fixation: the effect of substitution at the ?-Lys426 position in MoFe-protein of Azotobacter vinelandii. MC Durrant, A Francis, DJ Lowe, WE Newton, K Fisher. Biochem. J. (2006) 397:261-270.
The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine. C Paraskevopoulou, SA Fairhurst, DJ Lowe, P Brick, Onesti. Mol. Micro. (2006) 59:795-806.
Vanadium(V) is reduced by the 'as isolated' nitrogenase Fe-protein at neutral pH. K Fisher, DJ Lowe, J Petersen. Chem. Commun. (2006) 2807-2809
On the purification and preliminary crystallographic analysis of Isoquinoline 1-oxidoreductase from Brevundimonas diminuta 7. DR Boer, A Muller, S Fetzner, DL Lowe, MJ Romão Acta Cryst (2005) F61:137-140
Molecular characterization of human xanthine oxidoreductase: the enzyme is grossly deficient in molybdenum and substantially deficient in iron-sulphur centres. BLJ Godber, G Schwartz, RR Mendel, DJ Lowe, RC Bray, R Eisenthal, R Harrison Biochem. J. (2005) 388:501-508
Synthesis of new N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycines and N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycines esters. F Jourdan, JT Kaiser, DJ Lowe Synthetic Communications (2005) 35:2453-2466
Mn2+-adenosine nucleotide complexes in the presence of the nitrogenase iron-protein: detection of conformational rearrangements directly at the nucleotide binding site by EPR and 2D-ESEEM (two-dimensional electron spin-echo envelope modulation spectroscopy). J Petersen, C Gessner, K Fisher, CJ Mitchell, DJ Lowe, W Lubitz Biochem. J. (2005) 391:527-539
Potassium cyanate as an amino-dehydroxylating agent: Synthesis of aminooxypyrrole mono, dicarboxylic acid esters, and carbonitrile. F Jourdan, JT Kaiser, DJ Lowe Synthetic Commun. (2003) 33:2235-2241
Expression of Drosophila melanogaster xanthine dehydrogenase in Aspergillus nidulans and some properties of the recombinant enzyme. B Adams, DJ Lowe, AT Smith, C Scazzocchio, S Demais & RC Bray Biochem. J. (2002) 362, 223-229
Mo(V) co-ordination in the periplasmic nitrate reductase from Paracoccus pantotrophus probed by electron nuclear double resonance (ENDOR) spectroscopy. CS Butler, SA Fairhurst, SJ Ferguson, AJ Thomson, BC Berks, DJ Richardson & DJ Lowe Biochem. J. (2002) 363, 817-823
Probing the electronic structure of polynuclear metal clusters with total electron spin S>1/2 and significant zero-field splitting: Application to the clusters of nitrogenase MoFe-protein. J Petersen & DJ Lowe. Phys. Chem. Chem. Phys. (2002) 4, 2356-2364
Multiple Inequivalent Metal-Nucleotide Coordination Environments in the Presence of the VO2+-Inhibited Nitrogenase Iron Protein: pH-Dependent Structural Rearrangements at the Nucleotide Binding Site. J Petersen, K Fisher, CJ Mitchell & DJ Lowe Biochemistry (2002) 41, 13253-13263
Thiamine biosynthesis in Escherichia coli: isolation and initial characterization of the ThiGH complex. R Leonardi, SA Fairhurst, M Kriek, DJ Lowe & PL Roach FEBS Lett (2003) 539 95-99
A novel sterol 14 alpha-demethylase/ferredoxin fusion protein (MCCYP51FX) from Methylococcus capsulatus represents a new class of the cytochrome P450 superfamily. CJ Jackson, DC Lamb, TH Marezylo, AGS Warrilow, NJ Manning, DJ Lowe, DE Kelly, SL Kelly J Biol Chem (2002) 277:46959-46965
Electron Paramagnetic Resonance Analysis of Different Azotobacter vinelandii Nitrogenase MoFe-Protein Conformations Generated During Enzyme Turnover: Evidence for S=3/2 Spin States from Reduced MoFe-protein Intermediates. K Fisher, WE Newton & DJ Lowe. Biochemistry (2001) 40, 3333-3339.
Pre-steady-state Kinetic Analysis of Recombinant Arabidopsis NADH:Nitrate Reductase. L Skipper, WH Campbell, JA Mertens & DJ Lowe. J. Biol. Chem. (2001) 276, 26995-27001.
Single Turnover EPR Studies of Benzoyl-CoA Reductase. M Boll, G Fuchs & DJ Lowe Biochemistry (2001) 40, 7612-7620.
Reactions of Dimethylsulfoxide Reductase in the Presence of Dimethyl Sulfide and the Structure of the Dimethyl Sulfide-Modified Enzyme. RC Bray, B Adams, AT Smith, RL Richards, DJ Lowe & S Bailey Biochemistry (2001) 40, 9810-9820.
Mechanism of Reaction of Hydrogen Peroxide with Horseradish Peroxidase: Identification of Intermediates in the Catalytic Cycle. JN Rodríguez-López, DJ Lowe, J Hernández-Ruiz, ANP Hiner, F García-Cánovas & RNF Thorneley J. Am. Chem. Soc. (2001) 123, 11838-11847
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