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Researchers at UCD

researcher

Paul Engel

Professor Emeritus

School of Biomolecular & Biomedical Science
Conway Institute
Belfield Dublin 4

Tel: +353 1 7166764
Email: paul.engel@ucd.ie

Professional

Honours and Awards

Year: 2001.
Title: Member of the Royal Irish Academy

Associations

Association: Life Sciences Committee, Royal Irish Academy, Function/Role: Chairman
Association: European Federation of Biotechnology, Section on Applied Biocatalysis, Function/Role: Irish Representative

Patents

Patent 5,798,234 : Method for the Directed Modification of Enzymes, Modified Enzymes and Their Use(1998)
Patent S2005/0305 : Amino Acid Dehydrogenase-Derived Biocatalysts(2005)
     

Committees

Committee : Life Sciences Committee

Employment

Employer: University of Sheffield
Position: Senior Research Fellow
Employer: University of Hong Kong
Position: Viisiting Professorship
Employer: University College Dublin
Position: Professor
Employer: University of Michigan
Position: SERC/NATO Research Fellowship and Fulbright Hays Scholarship
Employer: University of Sheffield
Position: Lecturer in Biochemistry
Employer: University of Michigan
Position: Visiting Researcher
Employer: University of Leicester
Position: Visiting Researcher
Employer: University College Dublin
Position: Head of Department of Biochemistry
Employer: Krebs Institute for Biomolecular Research
Position: Founding Director

Education

Year 1965 Institution: Oxford University, UK
Qualification: BA Subject:
Year 1968 Institution: Oxford University, UK
Qualification: MA Subject:
Year 1968 Institution: Oxford University, UK
Qualification: DPhil Subject:
       

Other Activities

Chosen Irish Representative European Section on Applied Biocatalysis (European Federation of Biotechnology)  - 2006

Publications

Books

P.C. Engel.; (1995) Labfax Enzymology. *: BIOS Scientific Publishers. [Details]
Paul C. Engel & Peter Taylor; (1985) The regulation of enzyme-catalysed reactions in biological systems. S342 Topic Study 1. A study unit for the Open University Chemistry course. *: Open University. [Details]
R.C. Bray, P.C. Engel & S.G. Mayhew; (1984) Flavins and Flavoproteins. Berlin: de Gruyter. [Details]
Paul C. Engel; (1981) Enzyme Kinetics: The Steady-state Approach, 2nd edition. London: Chapman & Hall. [Details]
Paul C. Engel; (1977) Enzyme Kinetics: The Steady-state Approach. London: Chapman & Hall. [Details]

Book Chapters

Engel, P.C and Paradisi, F.; (2010) 'Novel enzymes for biotransformation and resolution of alpha-amino acids' In: J.C Vederas (eds). Comprehensive Natural Product 2 Chemistry and Biology. Oxford: Elsevier. , pp.71-90 [Details]
Conway,P. and Paradisi, F. and Engel, P.C.; (2010) 'Synthesis of substituted derivatives of L-phenylalanine and of other non-natural L-amino acids using engineered mutants of phenylalanine dehydrogenase' In: John Whittal & Peter W. Sutton (eds). Practical Methods in Biocatalysis and Biotransformations. Oxford: John Wiley. , pp.314-317 [DOI] [Details]
Paul C. Engel; (1984) 'Enzyme Kinetics. Chapter 7' In: M. I. Page (eds). The Chemistry of Enzyme Action, Vol.6 of New Comprehensive Biochemistry. *: Elsevier. [Details]
 

Peer Reviewed Journals

Sharkey, M. A.,Engel, P. C.; (2009) 'Modular coenzyme specificity: A domain-swopped chimera of glutamate dehydrogenase'. Proteins-Structure Function and Bioinformatics, 77 (2):268-278. [Details]
Wang, X. T.,Engel, P. C.; (2009) 'Clinical mutants of human glucose 6-phosphate dehydrogenase: Impairment of NADP(+) binding affects both folding and stability'. Biochimica Et Biophysica Acta-Molecular Basis of Disease, 1792 (8):804-809. [Details]
Chen, S. H.,Engel, P. C.; (2009) 'Efficient screening for new amino acid dehydrogenase activity: Directed evolution of Bacillus sphaericus phenylalanine dehydrogenase towards activity with an unsaturated non-natural amino acid'. Journal of Biotechnology, 142 (2):127-134. [Details]
Wang, X. T.,Engel, P. C.; (2009) 'An optimised system for refolding of human glucose 6-phosphate dehydrogenase'. Bmc Biotechnology, 9 . [Details]
Walsh DM, Sala Frigerio C, Kukar TL, Engel PC, Golde TE, ; (2009) 'An NSAID-like compound, FT-9, preferentially inhibits gamma-secretase cleavage of APP compared to its effect on APLP1'. Biochemistry, (NA). [DOI] [Details]
Engel, P.C. (2011) 'A marriage full of surprises: forty-five years living with glutamate dehydrogenase'. Neurochemistry International, 59 (4):489-494. Available Online [DOI] [Details]
Carrigan JB and Engel PC ; (2007) ''Probing the determinants of coenzyme specificity in Peptostreptococcus asaccharolyticus glutamate dehydrogenase by site-directed mutagenesis''. FEBS JOURNAL, 274 :5167-5174. [Details]
Hamza MA, Martin SR, Engel PC; (2007) ''The contribution of tryptophan residues to conformational changes in clostridial glutamate dehydrogenase - W64 and W449 as mediators of the cooperative reponse to glutamate''. FEBS JOURNAL, 274 :4126-4134. [Details]
Hamza MA, Engel, PC ; (2007) ''Enhancing long-term stability in mesophilic glutamate dehydrogenase from Clostridium symbiosum by eliminating cysteine residues''. Enzyme and Microbial Technology, 41 :706-710. [Details]
Muaawia Hamza, Paul C. Engel ; (2008) ''Homotropic allosteric control in clostridial glutamate dehydrogenase: different mechanisms for glutamate and NAD+ ?''. FEBS LETTERS, 582 :1816-1820. [Details]
Michael A Sharkey and Paul C Engel; (2008) 'Apparent negative cooperativity and substrate inhibition in overexpressed glutamate dehydrogenase from Escherichia coli'. FEMS Microbiol Letters, 281 :132-139. [Details]
Yuxiang Huang, Mei Yee Choi, Shannon Wing Ngor Au, Deborah Man Yee Au, Veronica Min Sien Lam, Paul C Engel. ; (2008) 'Defective protein folding, a mechanism underlying two clinically different human glucose 6-phosphate dehydrogenase variants, G6PD Plymouth and G6PD Mahidol'. Molecular Genetics and Metabolism, . [Details]
J.B. Carrigan & P.C. Engel; (2007) 'Probing the determinants of coenzyme specificity in Peptostreptococcus asaccharolyticus glutamate dehydrogenase by site-directed mutagenesis'. FEBS JOURNAL, 274 :5157-5174. [Details]
S. Chen & P.C. Engel.; (2007) 'An engineered mutant, L307V, of phenylalanine dehydrogenase from Bacillus sphaericus: high activity and stability in organic-aqueous solvent mixtures and utility for synthesis of non-natural L-amino acids'. Enzyme and Microbial Technology, 40 :1407-1411. [Details]
M. Hamza, S.R. Martin & P.C. Engel.; (2007) 'The contribution of tryptophan residues to conformational changes in clostridial glutamate dehydrogenase: W64 and W449 as mediators of the cooperative response to glutamate'. Febs Journal, . [Details]
Paradisi, F; Collins, S; Maguire, AR; Engel, PC; ; (2007) 'Phenylalanine dehydrogenase mutants: Efficient biocatalysts for synthesis of non-natural phenylalanine derivatives'. Journal of Biotechnology, 128 (2):408-411. [Details]
M. Hamza & P.C. Engel; (2007) 'Enhancing Long-term Thermal stability in Mesophilic Glutamate Dehydrogenase from Clostridium symbiosum by Eliminating Cysteine Residues'. Enzyme and Microbial Technology, . [Details]
Wang, XT; Lam, VMS; Engel, PC; ; (2006) 'Functional properties of two mutants of human glucose 6-phosphate dehydrogenase, R393G and R393H, corresponding to the clinical variants G6PD Wisconsin and Nashville'. Biochimica Et Biophysica Acta-Molecular Basis of Disease, 1762 (8):767-774. [Details]
Faulkner, E; Barrett, M; Okor, S; Kieran, P; Casey, E; Paradisi, F; Engel, P; Glennon, B; ; (2006) 'Use of fed-batch cultivation for achieving high cell densities for the pilot-scale production of a recombinant protein (phenylalanine dehydrogenase) in Escherichia coli'. Biotechnology Progress, 22 (3):889-897. [Details]
Cainelli, G; Engel, PC; Galletti, P; Giacomini, D; Gualandi, A; Paradisi, F; ; (2005) 'Engineered phenylalanine dehydrogenase in organic solvents: homogeneous and biphasic enzymatic reactions'. Organic and Biomolecular Chemistry, 3 (24):4316-4320. [Details]
Carrigan, JB; Coughlan, S; Engel, PC; ; (2005) 'Properties of the thermostable glutamate dehydrogenase of the mesophilic anaerobe Peptostreptoccus asaccharolyticus purified by a novel method after over-expression in an Escherichia coli host'. Fems Microbiology Letters, 244 (1):53-59. [Details]
Ingoldsby, LM; Geoghegan, KF; Hayden, BM; Engel, PC; ; (2005) 'The discovery of four distinct glutamate dehydrogenase genes in a strain of Halobacterium salinarum'. Gene, 349 (NA):237-244. [Details]
Paradisi, F; Dean, JLE; Geoghegan, KF; Engel, PC; ; (2005) 'Spontaneous chemical reversion of an active site mutation: Deamidation of an asparagine residue replacing the catalytic aspartic acid of glutamate dehydrogenase'. Biochemistry, 44 (9):3636-3643. [Details]
O'Reilly, LP; Andresen, BS; Engel, PC; ; (2005) 'Two novel variants of human medium chain acyl-CoA dehydrogenase (MCAD) - K364R, a folding mutation, and R256T, a catalytic-site mutation resulting in a well-folded but totally inactive protein'. FEBS Journal, 272 (17):4549-4557. [Details]
Paradisi, F; Woolfson, R; Geoghegan, KF; Engel, PC; ; (2005) 'Identification of the residue responsible for catalysing regeneration of activity in the inactive glutamate dehydrogenase mutant D165N'. FEBS Letters, 579 (13):2830-2832. [Details]
Aherne, A; Kennan, A; Kenna, PF; McNally, N; Lloyd, DG; Alberts, IL; Kiang, AS; Humphries, MM; Ayuso, C; Engel, PC; Gu, JJ; Mitchell, BS; Farrar, GJ; Humphries, P; ; (2004) 'On the molecular pathology of neurodegeneration in IMPDH1-based retinitis pigmentosa'. Human Molecular Genetics, 13 (6):641-650. [Details]
Busca, P; Paradisi, F; Moynihan, E; Maguire, AR; Engel, PC; ; (2004) 'Enantioselective synthesis of non-natural amino acids using phenylalanine dehydrogenases modified by site-directed mutagenesis'. Organic and Biomolecular Chemistry, 2 (18):2684-2691. [Details]
Batoux, NE; Paradisi, F; Engel, PC; Migaud, ME; ; (2004) 'Novel nicotinamide adenine dinucleotide analogues as selective inhibitors of NAD+-dependent enzymes'. Tetrahedron, 60 (31):6609-6617. [Details]
O'Reilly, L; Bross, P; Corydon, TJ; Olpin, SE; Hansen, J; Kenney, JM; McCandless, SE; Frazier, DM; Winter, V; Gregersen, N; Engel, PC; Andresen, BS; ; (2004) 'The Y42H mutation in medium-chain acyl-CoA dehydrogenase, which is prevalent in babies identified by MS/MS-based newborn screening, is temperature sensitive'. European Journal of Biochemistry, 271 (20):4053-4063. [Details]
Ahearne, A; Kennan, A; Bowne, SJ; Daiger, SP; Engel, PC; Farrar, GJ; Kenna, PF; Humphries, P; ; (2003) 'Functional analysis of mutations in IMPDH1 gene implicated in RP10 form of retinitis pigmentosa'. Investigative Ophthalmology &Amp; Visual Science, 44 (NA):277-277. [Details]
Irwin, JA; Lynch, SV; Coughlan, S; Baker, PJ; Gudmundsson, HM; Alfredsson, GA; Rice, DW; Engel, PC; ; (2003) 'Alanine dehydrogenase from the psychrophilic bacterium strain PA-43: overexpression, molecular characterization, and sequence analysis'. Extremophiles, 7 (2):135-143. [Details]
Seah, SYK; Britton, KL; Rice, DW; Asano, Y; Engel, PC; ; (2002) 'Single amino acid substitution in Bacillus sphaericus phenylalanine dehydrogenase dramatically increases its discrimination between phenylalanine and tyrosine substrates'. Biochemistry, 41 (38):11390-11397. [Details]
Wang, XT; Au, SWN; Lam, VMS; Engel, PC; ; (2002) 'Recombinant human glucose-6-phosphate dehydrogenase'. European Journal of Biochemistry, 269 (14):3417-3424. [Details]
X.-T. Wang, S.W.N. Au, V.M.S. Lam & P.C. Engel; (2002) 'Recombinant human glucose-6-phosphate dehydrogenase: evidence for a rapid-equilibrium random-order mechanism'. European Journal of Biochemistry, 269 :3417-3424. [Details]
Hayden, BM; Bonete, MJ; Brown, PE; Moir, AJG; Engel, PC; ; (2002) 'Glutamate dehydrogenase of Halobacterium salinarum: evidence that the gene sequence currently assigned to the NADP(+)-dependent enzyme is in fact that of the NAD(+)-dependent glutamate dehydrogenase'. Fems Microbiology Letters, 211 (1):37-41. [Details]
Irwin, JA; Gudmundsson, HM; Marteinsson, VT; Hreggvidsson, GO; Lanzetti, AJ; Alfredsson, GA; Engel, PC; ; (2001) 'Characterization of alanine and malate dehydrogenases from a marine psychrophile strain PA-43'. Extremophiles, 5 (3):199-211. [Details]
Wang, X. G., Britton, K. L., Stillman, T. J., Rice, D. W., and Engel, P. C.; (2001) 'Novel enzyme specificity: engineering of a monocarboxylic amino acid dehydrogenase with activity towards L-methionine by site-directed mutagenesis of a clostridial glutamate dehydrogenase gene'. European Journal of Biochemistry, 268 :5791-5799. [Details]
Wang, X. G., Britton, K. L., Stillman, T. J., Rice, D. W., and Engel, P. C.; (2001) 'Novel enzyme specificity: engineering of a monocarboxylic amino acid dehydrogenase with activity towards L-methionine by site-directed mutagenesis of a clostridial glutamate dehydrogenase gene'. European Journal of Biochemistry, 268 :5791-5799. [Details]
Goyal, A; Wang, XG; Engel, PC; ; (2001) 'Allosteric behaviour of 1 : 5 hybrids of mutant subunits of Clostridium symbiosum glutamate dehydrogenase differing in their amino acid specificity'. Biochemical Journal, 360 (NA):651-656. [Details]
Wang, XG; Britton, KL; Stillman, TJ; Rice, DW; Engel, PC; ; (2001) 'Conversion of a glutamate dehydrogenase into methionine/norleucine dehydrogenase by site-directed mutagenesis'. European Journal of Biochemistry, 268 (22):5791-5799. [Details]
Andresen, BS; Dobrowolski, SF; O'Reilly, L; Muenzer, J; McCandless, SE; Frazier, DM; Udvari, S; Bross, P; Knudsen, I; Banas, R; Chace, DH; Engel, P; Naylor, EW; Gregersen, N; ; (2001) 'Medium-chain Acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-Based prospective screening of newborns differ from those observed in patients with clinical symptoms: Identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency'. American Journal of Human Genetics, 68 (6):1408-1418. [Details]
Irwin, JA; Alfredsson, GA; Lanzetti, AJ; Gudmundsson, HM; Engel, PC; ; (2001) 'Purification and characterisation of a serine peptidase from the marine psychrophile strain PA-43'. Fems Microbiology Letters, 201 (2):285-290. [Details]
Hayden, BM; Engel, PC; ; (2001) 'Construction, separation and properties of hybrid hexamers of glutamate dehydrogenase in which five of the six subunits are contributed by the catalytically inert D165S'. European Journal of Biochemistry, 268 (5):1173-1180. [Details]
Coughlan, S; Wang, XG; Britton, KL; Stillman, TJ; Rice, DW; Chiaraluce, R; Consalvi, V; Scandurra, R; Engel, PC; ; (2001) 'Contribution of an aspartate residue, D114, in the active site of clostridial glutamate dehydrogenase to the enzyme's unusual pH dependence'. Biochimica Et Biophysica Acta-Protein Structure and Molecular Enzymology, 1544 (1-2):10-17. [Details]
Hayden, and Engel, P. C.; (2001) 'Construction, separation and properties of hybrid hexamers of glutamate dehydrogenase in which five of the six subunits are contributed by the catalytically inert D165S mutant'. European Journal of Biochemistry, 268 :1173-1180. [Details]
Andresen, B. S., Dobrowoloski, S. F., OReilly, L., Muenzer, J., McCandless, S. E., Frazier, D. M., Udvari, S., Bross, P., Knudsen, I., Banas, R., Chace, D. H., Engel, P., Naylor, E. W., and Gregersen, N.; (2001) 'Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterisation of a new, prevalent mutation that results in mild MCAD deficiency'. American Journal of Human Genetics, 68 :1408-1418. [Details]
Irwin, J. A., Alfredsson, G. A., Lanzetti, A. J., Gudmundsson, H. M., and Engel, P. C.; (2001) 'Purification and characterisation of a serine peptidase from the marine psychrophile strain PA-43'. Fems Microbiology Letters, 20 :285-290. [Details]
Irwin, J. A., Gudmundsson, H. M., Lanzetti, A. J., Alfredsson, G. A., and Engel P. C.; (2001) 'Characterisation of alanine and malate dehydrogenases from a marine psychrophile strain PA-43'. Extremophiles, 5 :199-211. [Details]
Parker, A; Engel, PC; ; (2000) 'Preliminary evidence for the existence of specific functional assemblies between enzymes of the beta-oxidation pathway and the respiratory chain'. Biochemical Journal, 345 (NA):429-435. [Details]
Aghajanian, S., Walsh, T. P., and Engel, P. C.; (1999) 'Specificity of coenzyme analogues and fragments in promoting or impeding the refolding of clostridial glutamate dehydrogenase '. Protein Science, 8 :866-872. [Details]
Parker, A; Engel, PC; ; (1999) '5,5 '-dithiobis-(2-nitrobenzoic acid) as a probe for a non-essential cysteine residue at the medium chain acyl-coenzyme a dehydrogenase binding site of the human 'electron transferring flavoprotein' (ETF)'. Journal of Enzyme Inhibition, 14 (5):381-390. [Details]
Aghajanian, S; Walsh, TP; Engel, PC; ; (1999) 'Specificity of coenzyme analogues and fragments in promoting or impeding the refolding of clostridial glutamate dehydrogenase'. Protein Science, 8 (4):866-872. [Details]
Hayden, BM; Dean, JLE; Martin, SR; Engel, PC; ; (1999) 'Chemical rescue at the catalytically disabled clostridial glutamate dehydrogenase mutant D165S by fluoride ion'. Biochemical Journal, 340 (NA):555-560. [Details]
Udvari, S; Bross, P; Andresen, BS; Gregersen, N; Engel, PC; ; (1999) 'Biochemical characterisation of mutations of human medium-chain acyl-CoA dehydrogenase'. Current Views of Fatty Acid Oxidation and Ketogenesis, 466 (NA):387-393. [Details]
Hayden, B. M., Dean, J. L. E., Martin, S. R., and Engel P. C.; (1999) 'Chemical rescue of the catalytically disabled clostridial glutamate dehydrogenase mutant D165S by fluoride ion'. Journal of Biochemistry, 340 :555-560. [Details]
Parker, A; Engel, PC; ; (1999) 'Formation of a human electron transferring flavoprotein - Medium chain acyl coenzyme A dehydrogenase complex, preliminary evidence from crosslinking studies'. Current Views of Fatty Acid Oxidation and Ketogenesis, 466 (NA):191-194. [Details]
Aghajanian, S., and Engel, P. C.; (1998) 'Use of protein engineering to explore subunit interactions in an allosteric enzyme: construction of inter-subunit hybrids in Clostridium symbiosum0 glutamate dehydrogenase'. Protein Engineering, 11 :569-575. [Details]
Scandurra, R; Consalvi, V; Chiaraluce, R; Politi, L; Engel, PC; ; (1998) 'Protein thermostability in extremophiles'. Biochimie, 80 (11):933-941. [Details]
Broadway, NM; Engel, PC; ; (1998) 'Novel methylenecyclopropyl-based acyl-CoA dehydrogenase inhibitor'. FEBS Letters, 437 (1-2):122-126. [Details]
Parker, A; Engel, PC; ; (1998) 'Chemical modification of histidine residues in human 'electron transferring flavoprotein' (ETP)'. Biochemical Society Transactions, 26 (3):272-272. [Details]
Aghajanian, S; Engel, PC; ; (1998) 'Use of protein engineering to explore subunit interactions in an allosteric enzyme: construction of inter-subunit hybrids in Clostridium symbiosum glutamate dehydrogenase'. Protein Engineering, 11 (7):569-575. [Details]
Britton, KL; Stillman, TJ; Yip, KSP; Forterre, P; Engel, PC; Rice, DW; ; (1998) 'Insights into the molecular basis of salt tolerance from the study of glutamate dehydrogenase from Halobacterium salinarum'. Journal of Biological Chemistry, 273 (15):9023-9030. [Details]
Basso, LA; Engel, PC; Walmsley, AR; ; (1998) 'Cooperativity between trimers of the hexameric glutamate dehydrogenase from Clostridium symbiosum'. Biochimica Et Biophysica Acta-Protein Structure and Molecular Enzymology, 1382 (2):345-350. [Details]
Etchegaray, A; Dieckmann, R; Engel, PC; Turner, G; von Dohren, H; ; (1998) 'Group specific antibodies against the putative AMP-binding domain signature SGTTGXPKG in peptide synthetases and related enzymes'. Biochemistry and Molecular Biology International, 44 (2):235-243. [Details]
Aghajanian, S; Hovsepyan, M; Geoghegan, KF; Chrunyk, BA; Engel, PC; ; (1998) 'Probing the stability of the tertiary structure of glutamate dehydrogenase by limited proteolysis'. Biochemical Society Transactions, 26 (1):26-26. [Details]
Goyal, A; Aghajanian, S; Hayden, BM; Wang, XG; Engel, PC; ; (1998) 'Construction and investigation of co-operativity in hybrids of norleucine- and glutamate-active subunits of clostridial glutamate dehydrogenase'. Biochemical Society Transactions, 26 (1):27-27. [Details]
Udvari, S; Bross, P; Andresen, BS; Gregersen, N; Engel, PC; ; (1998) 'Mutations of human medium-chain acyl-CoA dehydrogenase'. Biochemical Society Transactions, 26 (1):65-65. [Details]
Irwin, JA; Alfredsson, GA; Gudmundsson, HM; Engel, PC; ; (1998) 'Purification and properties of psychrophilic dehydrogenases'. Biochemical Society Transactions, 26 (1):72-72. [Details]
Parker, A; Engel, PC; ; (1998) 'Experimental evidence for the formation of a complex between butyryl coenzyme A dehydrogenase and the 'electron transferring flavoprotein', ETF'. Biochemical Society Transactions, 26 (1):73-73. [Details]
Dean, JLE; Colfen, H; Harding, SE; Rice, DW; Engel, PC; ; (1997) 'Alteration of the quaternary structure of glutamate dehydrogenase from Clostridium symbiosum by a single mutation distant from the subunit interfaces'. European Biophysics Journal With Biophysics Letters, 25 (5-6):417-422. [Details]
Wang, XG; Britton, LK; Baker, PJ; Rice, DW; Engel, PC; ; (1996) 'Improving the engineered activity of mutants of clostridial glutamate dehydrogenase towards monocarboxylic substrates: Substitution of Ala163 with glycine'. Biochemical Society Transactions, 24 (1):126-126. [Details]
Aghajanian, SA; Wang, XG; Engel, PC; ; (1996) 'In vitro construction of inter-subunit hybrids in Clostridium symbiosum glutamate dehydrogenase'. Biochemical Society Transactions, 24 (1):136-136. [Details]
Coughlan, S; Wang, XG; Britton, KL; Stillman, TJ; Rice, DW; Engel, PC; ; (1996) 'Preliminary functional studies of mutant D114N of Clostridium symbiosum glutamate dehydrogenase'. Biochemical Society Transactions, 24 (1):149-149. [Details]
AGHAJANIAN, SA; MARTIN, SR; ENGEL, PC; ; (1995) 'UREA-INDUCED INACTIVATION AND DENATURATION OF CLOSTRIDIAL GLUTAMATE-DEHYDROGENASE - THE ABSENCE OF STABLE DIMERIC OR TRIMERIC INTERMEDIATES'. Biochemical Journal, 311 (NA):905-910. [Details]
WANG, XG; ENGEL, PC; ; (1995) 'POSITIVE COOPERATIVITY WITH HILL COEFFICIENTS OF UP-TO-6 IN THE GLUTAMATE CONCENTRATION-DEPENDENCE OF STEADY-STATE REACTION-RATES MEASURED WITH CLOSTRIDIAL GLUTAMATE-DEHYDROGENASE AND THE MUTANT A163G AT HIGH PH'. Biochemistry, 34 (36):11417-11422. [Details]
WANG, XG; BRITTON, KL; BAKER, PJ; MARTIN, S; RICE, DW; ENGEL, PC; ; (1995) 'ALTERATION OF THE AMINO-ACID SUBSTRATE-SPECIFICITY OF CLOSTRIDIAL GLUTAMATE-DEHYDROGENASE BY SITE-DIRECTED MUTAGENESIS OF AN ACTIVE-SITE LYSINE RESIDUE'. Protein Engineering, 8 (2):147-152. [Details]
Seah, SYK; Britton, KL; Rice, DW; Asano, Y; Engel, PC; ; (2003) 'Kinetic analysis of phenylalanine dehydrogenase mutants designed for aliphatic amino acid dehydrogenase activity with guidance from homology-based modelling'. European Journal of Biochemistry, 270 (23):4628-4634. [Details]

Other Journals

Wang, X.T., Lam V.M.S. & Engel, P.C.; (2006) 'Functional properties of two mutants of human glucose 6-phosphate dehydrogenase, R393G and R393H, corresponding to the clinical variants G6PD Wisconsin and Nashville' Biochimica et Biophysica Acta (Molecular Basis of Disease) 1762 :767-774. [Details]
Paradisi, F., Collins, S., Maguire, A.R. & Engel, P.C.; (2006) 'The use of phenylalanine dehydrogenase mutants as efficient catalysts for the synthesis of non-natural amino acids: scale-up process' * . [Details]
Wang, X.T., Lam, V.M.S. & Engel, P.C.; (2005) 'Marked decrease in specific activity contributes to disease phenotype in two human glucose 6-phosphate dehydrogenase mutants, G6PDUnion and G6PDAndalus' Human Mutation MIB . [Details]
Busca P, Paradisi F, Moynihan E, Maguire AR, Engel PC. ; (2004) 'Enantioselective synthesis of non-natural amino acids using phenylalanine dehydrogenases modified by site-directed mutagenesis' Organic & Biomolecular Chemistry 2 (2691) . [Details]
                                                                                           

Research

Research Interests

Research carried out by my group focuses on various aspects of enzymes, especially those involved in oxidising amino acids, aiming at a molecular understanding of how they work. Typically this involves obtaining the enzymes in a highly purified state, usually after cloning the gene into a suitable host organism in order to achieve high levels of the enzyme protein.

Some of the work involves studying the enzyme mechanisms, seeking the structural basis of their catalytic activity and in particular aiming for a better understanding of how different protein subunits work together to provide sophisticated regulation of activity – e.g. in the allosteric control of glutamate dehydrogenase.

Other work, in part supported through Enterprise Ireland’s advanced technology research programme, is focused on practical applications. Modern gene technology makes it possible to alter and adapt enzymes, in search of useful new properties. The chemical industry needs good catalysts, and specifically it needs ‘chiral’ catalysts that can distinguish between left and right-handed versions of chemical molecules. Enzymes are ideal in this regard: they are extremely potent catalysts and they normally give 100% discrimination between left and right. The snag in the past has been that they were too expensive, too fragile and often worked only on the wrong compounds – i.e. biological compounds that might not match the chemist’s requirements. This line of research is now producing biocatalysts that are cheap, robust and above all can now work on a wider and more attractive range of chemical targets. This is primarily aimed at producing building blocks for the drug industry.

A third strand of this group’s research aims to discover the various ways in which genetic defects in enzymes cause disease.  G6PD (glucose 6-phosphate dehydrogenase), is defective in over 400 million people worldwide. The disease mainly affects red blood cells, causing anaemia, and is so prevalent because it coincidentally protects against malaria! Most of the disease mutations affect the long-term stability of the enzyme in the red cell which cannot replace damaged enzyme molecules. We are studying the folding of this enzyme. Another disease-related enzyme under study is IMPDH1. A defect in this enzyme is responsible for progressive blindness in one of the forms of retinitis pigmentosa. This particular form RP10 shows ‘negative dominant’ inheritance, so that getting the ‘bad’ gene from one parent only is sufficient to cause blindness. The research is aimed at understanding how this happens, with perhaps a chance of finding ways to slow or prevent loss of sight.

Finally, another aspect of the group’s research focuses on ‘extremophiles’; organisms that live in what, to us, seem very hostile environments (i.e. hot, cold, salty). The enzymes of these organisms have to be able to survive the conditions, otherwise the organisms themselves would die. Looking at the molecular adaptations that make this possible teaches us a lot about how proteins work, and some of these tough enzymes have highly desirable properties for practical application.

 

Recent Postgraduates

  • Mr. David Scanlon
  • Ms. Marina Capone
  • Mr. Muaawia Hamza
  • Ms. Sihong Chen
  • Ms. Marie Fagan
  • Ms. Izzy Ibrahim
  • Mr. Kalyana Charavarthy Venneti

 

 

 

 

 

 

Collaborators

Internal Collaborators


Dr. Brian Glennon
Dr. Francesca Paradisi
Dr. Dominic Walsh

External Collaborators

Dr. Steve Martin   NIMR Mill Hill
Prof. Steve Harding    National Centre for Macromolecular Hydrodynamics, Sutton Bonington, UK
Dr. Daria Giacomini and Prof.Gianfranco Cainelli, University of Bologna, Italy
Prof. David Rice, University of Sheffield, UK
Dr. Amir Khan, Trinity College Dublin
Prof. Anita Maguire, University College Cork
Dr. Xing-guo Wang, Hubei University, China
Dr. Ken Devine, London Metropolitan University

Dr. Sylke Muller, University of Glasgow