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Paul Engel

Professor

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

Biography

Paul Engel is an enzymologist/protein engineer. Educated in Hong Kong and then as a biochemist at Oxford, he did a D. Phil. in enzyme kinetics (1968) and a post-doc. on flavoproteins at the University of Michigan. He was Lecturer in Biochemistry at Sheffield from 1970, Reader in 1984 and founding Director of the inter-disciplinary Krebs Institute. He was also Programme Manager for the U.K. SERC Biotechnology Directorate's pioneering 'Protein Engineering Club' experiment in state/industry co-funding. Following a Royal Society Leverhulme Trust Research Fellowship back at Sheffield and a Visiting Professorship at the University of Hong Kong, he took up the Chair of Biochemistry at University College Dublin in 1994.  With two professorial colleagues he spearheaded UCD's successful bid for government (PRTLI) funding of the Conway Institute, moving Biochemistry to a modern, purpose-built research building. Officially retired in 2009 as a member of teaching staff, Prof. Engel was supported 2006 - 2011 by a 5-year SFI Fellowship Award. Latterly, with ongoing support from SFI and from industry, his international research team at the Conway Institute, continues to focus on diverse aspects of oxidative enzymes and transaminases, with emphasis on engineering novel biocatalysts, understanding inter-subunit communication in allosteric enzymes, and explaining enzyme deficiency diseases at a molecular level. Understanding and controlling protein folding is a newer aspect of the group's research intersecting the other topics at various points. Paul Engel has taken a keen and active interest in public awareness of science and started a programme at UCD for training Ph. D. students in presenting science to the public, leading on to a high-profile competition. Originally the 'Merville Lay Seminars', this became 'Accesscience'. Paul was an elected member of UCD's Governing Authority 2005 - 2009.Elected a Member of the Royal Irish Academy in 2001, he has also Chaired its Life Sciences Committee. In 2010 he was awarded the Biochemical Irish Area Section's Medal for outstanding research carried out in Ireland. 

Professional

Honours and Awards

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

Associations

Association: Council of the Royal Irish Academy , Function/Role:
Association: Royal Irish Academy, Function/Role: Vice-president
Association: Life Sciences Committee, Royal Irish Academy, Function/Role: Member and Past 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)
   

Conference Contributions

P.C. Engel; (2007) A presentation on the use of engineered biocatalysts to produce chiral non-natural amino acids as pharmaceutical synthons. [Plenary Lecture], 13th European Congress on Biotechnology, Barcelona , 16-SEP-07 - 19-SEP-07.
Engel, P.; (2001) Substrate Channelling in Fatty Acid Oxidation. [Invited Oral Presentation], Biochemical Society Meeting, York , 01-DEC-01 - 01-DEC-01.

Committees

Committee : Royal Irish Academy Life Sciences Committee
           

Other Activities

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

Publications

Books

Paul C. Engel; (2009) Pain-free Biochemistry. Chichester: Wiley-Blackwell. [Details]
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]

Edited Books

R.C. Bray, P.C. Engel & S.G. Mayhew (Ed.). (1984) Flavins and Flavoproteins. Berlin: de Gruyter. [Details]

Peer Reviewed Journals

Sharkey MA, Gori A, Capone M and Engel PC (2012) 'Reversal of the extreme coenzyme selectivity of Clostridium symbiosum glutamate dehydrogenase'. FEBS Journal, 279 (17):3003-3009. [DOI] [Details]
Nayla Munawar & Paul C. Engel (2012) 'Overexpression in a non-native halophilic host and biotechnological potential of NAD+-dependent glutamate dehydrogenase from Halobacterium salinarum strain NRC-36014'. Extremophiles, . [DOI] [Details]
Xuejing Yu, Julia Bresser, Iris Schall, Ivana Djurdjevic, Wolfgang Buckel, Xingguo Wang and Paul C. Engel (2012) 'Development of a satisfactory and general continuous assay for aminotransferases by coupling with (R)-2-hydroxyglutarate dehydrogenase'. Analytical Biochemistry, 431 (2):127-131. Available Online [DOI] [Details]
Joanna Griffin and Paul C. Engel (2011) 'An Examination by Site-Directed Mutagenesis of Putative Key Residues in the Determination of Coenzyme Specificity in Clostridial N A D + -Dependent Glutamate Dehydrogenase'. Enzyme Research, 2011 . Available Online [DOI] [Details]
Xiao-tao Wang, Brian Mion, Aileen Aherne and Paul C. Engel (2011) 'Molecular recruitment as a basis for negative dominant inheritance? Propagation of misfolding in oligomers of IMPDH1, the mutated enzyme in the RP10 form of retinitis pigmentosa'. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1812 (11):1472-1476. Available Online [Details]
Oliveira, TF,Carrigan, JB,Hamza, MA,Sharkey, MA,Engel, PC,Khan, AR; (2010) 'Crystallization and preliminary structural analyses of glutamate dehydrogenase from Peptoniphilus asaccharolyticus'. Acta Crystallographica Section F, 66 :523-526. [DOI] [Details]
Aparicio, IM,Marin-Menendez, A,Bell, A,Engel, PC; (2010) 'Susceptibility of Plasmodium falciparum to glutamate dehydrogenase inhibitors-A possible new antimalarial target'. Molecular and Biochemical Parasitology, 172 :152-155. [DOI] [Details]
J. Griffin & P.C. Engel; (2010) 'The -SH Protection Method for Determining Accurate Kd Values for Enzyme-coenzyme Complexes of a Series of Mutant Variants of NAD+-dependent Glutamate Dehydrogenase and Engineered Mutants: Evidence for Non-productive NADPH Complexes'. Enzyme Research, 5 . [DOI] [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]
Sharkey, MA,Engel, PC; (2009) 'Modular coenzyme specificity: A domain-swopped chimera of glutamate dehydrogenase'. Proteins, 77 :268-278. [DOI] [Details]
Chen, SH,Engel, PC; (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 :127-134. [DOI] [Details]
Frigerio, CS,Kukar, TL,Fauq, A,Engel, PC,Golde, TE,Walsh, DM; (2009) 'An NSAID-like Compound, FT-9, Preferentially Inhibits gamma-Secretase Cleavage of the Amyloid Precursor Protein Compared to Its Effect on Amyloid Precursor-like Protein 1'. Biochemistry, 48 :10894-10904. [DOI] [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]
Paradisi, F,Conway, PA,Maguire, AR,Engel, PC; (2008) 'Engineered dehydrogenase biocatalysts for non-natural amino acids: efficient isolation of the D-enantiomer from racemic mixtures'. Org Biomol Chem, 6 :3611-3615. [DOI] [Details]
Huang, YX,Choi, MY,Au, SWN,Au, DMY,Lam, VMS,Engel, PC; (2008) 'Purification and detailed study of two clinically different human glucose 6-phosphate dehydrogenase variants, G6PD(Plymouth) and G6PD(Mahidol): Evidence for defective protein folding as the basis of disease'. Gene, 93 :44-53. [DOI] [Details]
Hamza, MA,Engel, PC; (2008) 'Homotropic allosteric control in clostridial glutamate dehydrogenase: Different mechanisms for glutamate and NAD(+)?'. FEBS Letters, 582 :1816-1820. [DOI] [Details]
Carrigan, JB,Engel, PC; (2008) 'The structural basis of proteolytic activation of bovine glutamate dehydrogenase'. PROTEIN SCI, 17 :1346-1353. [DOI] [Details]
Wang, X. T.,Chan, T. F.,Lam, V. M. S.,Engel, P. C.; (2008) 'What is the role of the second "structural" NADP(+)-binding site in human glucose 6-phosphate dehydrogenase?'. Protein Science, 17 (8):1403-1411. Available Online [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]
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]
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]
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]
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. Available Online [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]
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]
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]
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 :2830-2832. [DOI] [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]
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]
Aghajanian, S,Hovsepyan, M,Geoghegan, KF,Chirunyk, BA,Engel, PC; (2003) 'A thermally sensitive loop in clostridial glutamate dehydrogenase detected by limited proteolysis'. J BIOL CHEM, 278 :1067-1074. [DOI] [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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
Stillman, TJ,Migueis, AMB,Wang, XG,Baker, PJ,Britton, KL,Engel, PC,Rice, DW; (1999) 'Insights into the mechanism of domain closure and substrate specificity of glutamate dehydrogenase from Clostridium symbiosum'. Journal of Molecular Biology, 285 :875-885. [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]
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]
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]
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]
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]
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]
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]
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 :569-575. [Details]
Broadway, NM; Engel, PC; ; (1998) 'Novel methylenecyclopropyl-based acyl-CoA dehydrogenase inhibitor'. FEBS Letters, 437 (1-2):122-126. [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]
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]
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]
Goyal, A,Aghajanian, S,Hayden, BM,Wang, XG,Engel, PC; (1997) 'Intersubunit communication in hybrid hexamers of K89L/A163G/S380A and C320S mutants of glutamate dehydrogenase from Clostridium symbiosum'. Biochemistry, 36 :15000-15005. [Details]
Aghajanian, S,Engel, PC; (1997) 'Re-activation of Clostridium symbiosum glutamate dehydrogenase from subunits denatured by urea'. Biochem J, 326 :649-655. [Details]
Baker, PJ,Waugh, ML,Wang, XG,Stillman, TJ,Turnbull, AP,Engel, PC,Rice, DW; (1997) 'Determinants of substrate specificity in the superfamily of amino acid dehydrogenases'. Biochemistry, 36 :16109-16115. [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]
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; 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]
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]

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.; (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]
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]
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]
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]

Conference Publications

Faulkner, E., Barrett, M., Okor, S., Paradisi, F., Engel, P. & Glennon, B.; (2005) The use of fed batch cultivation for achieving high cell densities for the pilot scale production of a recombinant protein (Phenylalanine dehydrogenase) in Escherichia coli (oral communication) AIChE Annual Meeting Cincinnati, USA, , 30-OCT-05 - 04-NOV-05 [Details]
Faulkner, E., Barrett, M., Okor, S., Paradisi, F., Engel, P. & Glennon, B.; (2005) The use of fed batch cultivation for achieving high cell densities for the pilot scale production of a recombinant protein (Phenylalanine dehydrogenase) in Escherichia coli AIChE Annual Meeting Cincinnati, USA, , 30-OCT-05 - 04-NOV-05 , pp.9086-9095 [Details]
                                                                                         

Research

Research Interests

Research carried out by my group focuses on various aspects of enzymes, especially those involved in oxidising or transaminating 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, supported through Enterprise Ireland's Advanced Technology Research Programme and later by a Science Foundation Ireland Fellowship, has 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. Another application, requiring narrow specificity, is in diagnostic tests and this is being done through a campus company, Enzolve Technologies Ltd. with a focus on neonatal screening. The engineering of novel biocatalysts combines two approaches, knowledge-based, site-directed mutagenesis and random mutation supported by high-throughput screening. in the latter context the group is pioneering a new approach to single-cell screening of multiply-mutated gene libraries.
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. and looking for ways to stabilise it first in vitro and ultimately in human patients. 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.

Research Projects

Sponsor : Irish Research Council for Science Engineering and Technology (IRCSET)
Title : Mutating transaminase enzymes to make valuable amino acid building blocks for pharmaceutical synthesis
Start Date / End Date : 01-JUL-10 / 30-JUN-14
Sponsor : University College Dublin (UCD)
Title : M.Sc. Biotechnology research supervision
Start Date / End Date : 06-MAY-11 / 30-JUN-14
Sponsor : University College Dublin (UCD)
Title : Engineering new properties in phenylalanine dehydrogenase
Start Date / End Date : 01-SEP-11 / 31-AUG-12
Sponsor : Johnson Matthey plc
Title : Novel Biocatalysts Derived through Genetic Modification of Enzymes by Random Mutagenesis Assisted by Single-cell Screening
Start Date / End Date : 01-SEP-11 / 28-FEB-13
Sponsor : Science Foundation Ireland (SFI)
Title : Novel single-cell screening procedure for generating industrial biocatalysts
Start Date / End Date : 01-JAN-12 / 31-DEC-12
   

Teaching

Teaching Philosophy

         

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. Kevin Devine, London Metropolitan University

Dr. Angus Bell, Trinity College Dublin,
Dr. Sylke Muller, University of Glasgow
Dr. Kieran Geoghegan, Pfizer Inc. Groton, CT, USA 
Dr. Marie Migaud, Queen's University, Belfast