Faculty of Biological Sciences

Prof Alan Berry

BSc, PhD 1983, Southampton.
Professor in Molecular Enzymology
School of Molecular and Cellular Biology

Background: Postdoctoral work at ETH-Zurich and the University of Cambridge. Appointed lecturer 1994; Senior Lecturer 1997.

Contact:  Astbury 10.108 | +44(0) 113 34 33158 | email address for  

You can read more about Prof Berry's interests here:
www.astbury.leeds.ac.uk/People/staffpage.php?StaffID=ABe
bmbsgi10.leeds.ac.uk/

Research Interests

Engineering proteins for new functions

Protein engineering is a powerful tool for the study of the relationship between structure and function of enzymes and has important applications in the design of new enzymes. Both rational redesign and directed evolutionary approaches are being used in my laboratory to alter the specificity and chemistry of selected enzymes.

The fructose bisphosphate aldolases are important targets for engineering as new catalysts for stereospecific carbon-carbon bond formation. The roles of selected amino acids in the reaction mechanism of the enzyme have been elucidated in my laboratory and crystallography of the enzyme (with Dr Hunter, Dundee) is now enabling us to rationally redesign the enzyme for new substrate specificity. We are also using directed evolution to evolve novel enzymes for use in biocatalysis. These enzymes are being created by DNA shuffling or STEPing and are then subjected to rigourous analysis by a wide range of enzymological techniques such as kinetics, ESI-MS, CD, FTIR, NMR and X-ray crystallography.

Similar approaches are being used with the tagatose bisphosphate aldolase, N-acetylneuraminate lyase and N-acetylneuraminate synthase. These latter two enzymes are involved in the biosynthesis of sialic acid, an important molecule in many recognition events. Our experiments are aimed at understanding the functioning of these important enzymes and their redesign to act as catalysts for the synthesis of useful analogs of sialic acid (with Dr Nelson, Chemistry).

Our research is supported by BBSRC and The Wellcome Trust.

 

Faculty Research and Innovation


Studentship information

Undergraduate project topics:

  • Altering enzymes for new functions by random mutagenesis
    Keywords: PCR, forced evolution, screening, recombinant DNA methods (Laboratory)
  • Altering enzymes by rational redesign
    Keywords: PCR, site-directed mutagenesis, protein purification, recombinant DNA methods, enzyme kinetics (Laboratory)
  • Mechanism of enzyme action
    Keywords: Enzyme assays, enzyme purification, kinetics (Laboratory)

Postgraduate studentship areas:

  • Engineering Proteins for new functions by Directed Evolution

See also:

Admin roles

External Examiner (taught course): York
FBS FTSEC
FBS Graduate School Committee
FBS UGTSEC
UG Programme Leader: Biochemistry and JH

Modules taught

BIOC1301 - Intro Inte Biochem Mol Process
BIOC1302 - Intro Biochem Practical Skills
BIOC1303 - Intro Biochem Problem Solving
BIOC2301 - Interm Integrated Biochemistry
BIOC2302 - Intermediate Biochem: Prac
BIOC2303 - Intermediate Biochem: Skills
BIOC3111/12/13 a - Advanced Topics I (intro lecture)
BIOC3160 - Lab/Lit/Comp Research Project
BIOC3221/22/23 a - ATU 25 - Natural Product Biosynthesis
BIOC3221/22/23/31/32/33 - ATU intro lecture
BIOC3231/32/33 a - ATU 10 - Directed evolution
BIOC3231/32/33 b - ATU 33 - Synthetic Biology
BIOL3399 - Extended Research Project Preparation
BIOW5907X - Biocatalysis

Committees

Member of Faculty Taught Student Education Committee
Member of Graduate School Committee
Member of Undergraduate School Taught Student Education Committee

Daniels AD; Campeotto I; van der Kamp MW; Bolt AH; Trinh CH; Phillips SE; Pearson AR; Nelson A; Mulholland AJ; Berry A Reaction mechanism of N-acetylneuraminic acid lyase revealed by a combination of crystallography, QM/MM simulation, and mutagenesis. ACS Chem Biol 9 1025-1032, 2014
DOI:10.1021/cb500067z
View abstract

Windle CL; Muller M; Nelson A; Berry A Engineering aldolases as biocatalysts Current Opinion in Chemical Biology 19 25-33, 2014
DOI:10.1016/j.cbpa.2013.12.010
View abstract

Yi D; He N; Kickstein M; Metzner J; Weiss M; Berry A; Fessner W-D Engineering of a Cytidine 5 '-Monophosphate-Sialic Acid Synthetase for Improved Tolerance to Functional Sialic Acids ADVANCED SYNTHESIS&CATALYSIS 355 3597-3612, 2013
DOI:10.1002/adsc.201300568

Timms N; Windle CL; Polyakova A; Ault JR; Trinh CH; Pearson AR; Nelson A; Berry A Structural insights into the recovery of aldolase activity in N-acetylneuraminic acid lyase by replacement of the catalytically active lysine withγ-thialysine by using a chemical mutagenesis strategy. Chembiochem 14 474-481, 2013
DOI:10.1002/cbic.201200714
View abstract

Kinnell A; Harman T; Nelson A; Berry A; Bingham M Development of an organo- and enzyme-catalysed one-pot, sequential three-component reaction Tetrahedron 68 7719-7722, 2012
DOI:10.1016/j.tet.2012.02.010
View abstract

Timms N; Daniels AD; Berry A; Nelson A 7.3 Directed Evolution and (Semi-) Rational Design Strategies for the Creation of Synthetically useful, Stereoselective Biocatalysts Comprehensive Chirality 7 21-45, 2012
DOI:10.1016/B978-0-08-095167-6.00703-5
View abstract

Berry A; Timms, N; Daniels, AD; Nelson, A Directed Evolution and (Semi-) Rational Design Strategies for the Creation of Synthetically useful, Stereoselective Biocatalysts. In Comprehensive Chirality , 2012

Campeotto I; Bolt AH; Harman TA; Dennis C; Trinh CH; Phillips SEV; Nelson A; Pearson AR; Berry A Structural Insights into Substrate Specificity in Variants of N-Acetylneuraminic Acid Lyase Produced by Directed Evolution J MOL BIOL 404 56-69, 2010
DOI:10.1016/j.jmb.2010.08.008

Horsfall LE; Nelson A; Berry A Identification and characterization of important residues in the catalytic mechanism of CMP-Neu5Ac synthetase from Neisseria meningitidis FEBS J 277 2779-2790, 2010
DOI:10.1111/j.1742-4658.2010.07696.x

Tunio SA; Oldfield NJ; Berry A; Ala'Aldeen DAA; Wooldridge KG; Turner DPJ The moonlighting protein fructose-1, 6-bisphosphate aldolase of Neisseria meningitidis: surface localization and role in host cell adhesion MOL MICROBIOL 76 605-615, 2010
DOI:10.1111/j.1365-2958.2010.07098.x

Campeotto I; Carr SB; Trinh CH; Nelson AS; Berry A; Phillips SEV; Pearson AR Structure of an Escherichia coli N-acetyl-D-neuraminic acid lyase mutant, E192N, in complex with pyruvate at 1.45 angstrom resolution ACTA CRYSTALLOGR F 65 1088-1090, 2009
DOI:10.1107/S1744309109037403

Bolt A; Berry A; Nelson A Directed evolution of aldolases for exploitation in synthetic organic chemistry ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 474 318-330, 2008
DOI:10.1016/j.abb.2008.01.005

Burnley BT; Kalverda AP; Paisey SJ; Berry A; Homans SW Hadamard NMR spectroscopy for relaxation measurements of large (>35 kDa) proteins J BIOMOL NMR 39 239-245, 2007
DOI:10.1007/s10858-007-9192-4

Williams GJ; Woodhall T; Farnsworth LM; Nelson A; Berry A Creation of a pair of stereochemically complementary biocatalysts. J Am Chem Soc 128 16238-16247, 2006
DOI:10.1021/ja065233q
View abstract

Woodhall T; Williams G; Berry A; Nelson A Synthesis of screening substrates for the directed evolution of sialic acid aldolase: towards tailored enzymes for the preparation of influenza A sialidase inhibitor analogues. Org Biomol Chem 3 1795-1800, 2005
DOI:10.1039/b501503k
View abstract

Williams GJ; Woodhall T; Nelson A; Berry A Structure-guided saturation mutagenesis of N-acetylneuraminic acid lyase for the synthesis of sialic acid mimetics Protein Engineering Design and Selection 18 239-246, 2005
DOI:10.1093/protein/gzi027
View abstract

Woodhall T; Williams G; Berry A; Nelson A Creation of a tailored aldolase for the parallel synthesis of sialic acid mimetics ANGEW CHEM INT EDIT 44 2109-2112, 2005
DOI:10.1002/anie.200462733

Williams GJ; Nelson AS; Berry A Directed evolution of enzymes for biocatalysis and the life sciences Cellular and Molecular Life Sciences 61 3034-3046, 2004

Hao J; Berry A A thermostable variant of fructose bisphosphate aldolase constructed by directed evolution also shows increased stability in organic solvents. Protein Eng Des Sel 17 689-697, 2004
DOI:10.1093/protein/gzh081
View abstract

Williams GJ; Domann S; Nelson A; Berry A Modifying the stereochemistry of an enzyme-catalyzed reaction by directed evolution P NATL ACAD SCI USA 100 3143-3148, 2003
DOI:10.1073/pnas.0635924100

Hall DR; Kemp LE; Leonard GA; Marshall K; Berry A; Hunter WN The organization of divalent cations in the active site of cadmium Escherichia coli fructose-1,6-bisphosphate aldolase ACTA CRYSTALLOGR D 59 611-614, 2003
DOI:10.1107/S0907444902023661

Suryanti V; Nelson A; Berry A Cloning, over-expression, purification, and characterisation of N-acetylneuraminate synthase from Streptococcus agalactiae PROTEIN EXPRES PURIF 27 346-356, 2003

Hall DR; Bond CS; Leonard GA; Watt I; Berry A; Hunter WN Structure of tagatose-1,6-bisphosphate aldolase - Insight into chiral discrimination, mechanism, and specificity of class II aldolases J BIOL CHEM 277 22018-22024, 2002
DOI:10.1074/jbc.M202464200

Zgiby S; Plater AR; Bates MA; Thomson GJ; Berry A A functional role for a flexible loop containing Glu182 in the class II fructose-1,6-bisphosphate aldolase from Escherichia coli J MOL BIOL 315 131-140, 2002
DOI:10.1006/jmbi.2001.5237

Hilcenko C; Berry A; Homans S; Kalverda A; Kupce E NMR investigation of the dynamics of the 78kDa class II fructose-1,6-bisphosphate aldolase BIOPHYS J 82 137A-137A, 2002

Zgiby SM; Thomson GJ; Qamar S; Berry A Exploring substrate binding and discrimination in fructose 1,6-biphosphate and tagatose 1,6-biphosphate aldolases European Journal of Biochemistry 267 1858-1868, 2000

Hall DR; Leonard GA; Reed CD; Watt CI; Berry A; Hunter WN The crystal structure of Escherichia coli Class II fructose-1,6-biphosphate aldolase in complex with phosphoglycolohydroxamate reveals details of mechanism and specificity Journal of Molecular Biology 287 383-394, 1999

Plater A; Zgiby SM; Thomson GJ; Qamar S; Wharton CW; Berry A Conserved residues in the mechanism of the E.coli classII FBP-aldolase Journal of Molecular Biology 285 843-855, 1999

Thomson GJ; Howlett GJ; Ashcroft AE; Berry A The dhnA gene of Escherichia coli encodes a class I fructose bisphosphate aldolase. Biochem J 331 ( Pt 2) 437-445, 1998
View abstract

Qamar S; Marsh K; Berry A Identification of arginine 331 as an important active site residue in the Class II fructose-1,6-bisphosphate aldolase of Escherichia coli Protein Science 5 154-161, 1996

Cooper J; Leonard GA; McSweeney SM; Thompson AW; Naismith JH; Qamar S; Plater A; Berry A; Hunter WN The crystal structure of a class II fructose-1,6-bisphosphate aldolase shows a novel binuclear metal-binding active site embedded in a familiar fold Structure 4 1303-1315, 1996

BERRY A; PLATER A; QAMAR S SUBSTRATE RECOGNITION IN THE FRUCTOSE BISPHOSPHATE ALDOLASES FASEB J 9 A1460-A1460, 1995

Kitagawa Y; Leonard GA; Harrop SJ; Peterson MR; Hunter WN; Qamar S; Berry A Additional crystal forms of the E.coli Class II fructose-1,6-bisphosphate aldolase Acta Crystallographica. Section D: Biological Crystallography 51 833-834, 1995

Packman LC; Berry A A reactive, surface cysteine residue of the Class II fructose-1,6-bisphosphate aldolase of E.coli revealed by electrospray ionisation mass spectrometry European Journal of Biochemistry 227 510-515, 1995

Bashir A; Perham RN; Scrutton NS; Berry A Altering kinetic mechanism and enzyme stability by mutagenesis of the dimer interface of glutathione reductase Biochemical Journal 312 527-533, 1995

RIETVELD P; ARSCOTT LD; BERRY A; SCRUTTON NS; DEONARAIN MP; PERHAM RN; WILLIAMS CH REDUCTIVE AND OXIDATIVE HALF-REACTIONS OF GLUTATHIONE-REDUCTASE FROM ESCHERICHIA-COLI BIOCHEMISTRY-US 33 13888-13895, 1994

Berry A; Brenner SE A prototype computer system for de novo protein design. Biochem Soc Trans 22 1033-1036, 1994

Brenner SE; Berry A A quantitative methodology for the de novo design of proteins. Protein Sci 3 1871-1882, 1994
DOI:10.1002/pro.5560031026
View abstract

MITTL PRE; BERRY A; SCRUTTON NS; PERHAM RN; SCHULZ GE ANATOMY OF AN ENGINEERED NAD-BINDING SITE PROTEIN SCI 3 1504-1514, 1994

MITTL PRE; BERRY A; SCRUTTON NS; PERHAM RN; SCHULZ GE A DESIGNED MUTANT OF THE ENZYME GLUTATHIONE-REDUCTASE SHORTENS THE CRYSTALLIZATION TIME BY A FACTOR OF 40 ACTA CRYSTALLOGR D 50 228-231, 1994

Brenner SE; Berry A Protein design by optimization of a sequence-structure quality function. Proc Int Conf Intell Syst Mol Biol 2 44-52, 1994
View abstract

MITTL PRE; BERRY A; SCRUTTON NS; PERHAM RN; SCHULZ GE STRUCTURAL DIFFERENCES BETWEEN WILD-TYPE NADP-DEPENDENT GLUTATHIONE-REDUCTASE FROM ESCHERICHIA-COLI AND A REDESIGNED NAD-DEPENDENT MUTANT J MOL BIOL 231 191-195, 1993

Berry A; Marshall KE Identification of zinc-binding ligands in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli. FEBS Lett 318 11-16, 1993
View abstract

Scrutton NS; Deonarain MP; Berry A; Perham RN Cooperativity induced by a single mutation at the subunit interface of a dimeric enzyme: glutathione reductase. Science 258 1140-1143, 1992
View abstract

Eisenberg D; Perutz MF; Buckingham AD; Fersht AR; Marshall K; Dixon HBF; Berry A; Graf L; Thornton J; Blow DM General discussion Faraday Discussions 93 107-129, 1992
DOI:10.1039/FD9929300107

Naismith JH; Bailey S; Habash J; Harrop SJ; Hunter WN; Ferrara JD; Marshall K; Berry AJ; Dauter Z; Wilson KS Initiating a crystallographic study of a class II fructose-1,6-bisphosphate aldolase Journal of Molecular Biology 225 1137-1141, 1992
View abstract

Perham RN; Scrutton NS; Berry A New enzymes for old: redesigning the coenzyme and substrate specificities of glutathione reductase. Bioessays 13 515-525, 1991
DOI:10.1002/bies.950131005
View abstract

HENDERSON GB; MURGOLO NJ; KURIYAN J; OSAPAY K; KOMINOS D; BERRY A; SCRUTTON NS; HINCHLIFFE NW; PERHAM RN; CERAMI A ENGINEERING THE SUBSTRATE-SPECIFICITY OF GLUTATHIONE-REDUCTASE TOWARD THAT OF TRYPANOTHIONE REDUCTION P NATL ACAD SCI USA 88 8769-8773, 1991

Scrutton NS; Berry A; Deonarain MP; Perham RN Active site complementation in engineered heterodimers of Escherichia coli glutathione reductase created in vivo. Proc Biol Sci 242 217-224, 1990
DOI:10.1098/rspb.1990.0127
View abstract

Deonarain MP; Scrutton NS; Berry A; Perham RN Directed mutagenesis of the redox-active disulphide bridge in glutathione reductase from Escherichia coli. Proc Biol Sci 241 179-186, 1990
DOI:10.1098/rspb.1990.0083
View abstract

Scrutton NS; Berry A; Perham RN Redesign of the coenzyme specificity of a dehydrogenase by protein engineering. Nature 343 38-43, 1990
DOI:10.1038/343038a0
View abstract

Deonarain MP; Berry A; Scrutton NS; Perham RN Alternative proton donors/acceptors in the catalytic mechanism of the glutathione reductase of Escherichia coli: the role of histidine-439 and tyrosine-99. Biochemistry 28 9602-9607, 1989
View abstract

Berry A; Scrutton NS; Perham RN Switching kinetic mechanism and putative proton donor by directed mutagenesis of glutathione reductase. Biochemistry 28 1264-1269, 1989
View abstract

Scrutton NS; Berry A; Perham RN Engineering of an intersubunit disulphide bridge in glutathione reductase from Escherichia coli. FEBS Lett 241 46-50, 1988
View abstract

Perham RN; Berry A; Scrutton NS Flavoprotein disulphide oxidoreductases: protein engineering of glutathione reductase from Escherichia coli. Biochem Soc Trans 16 84-87, 1988

Scrutton NS; Berry A; Perham RN Purification and characterization of glutathione reductase encoded by a cloned and over-expressed gene in Escherichia coli. Biochem J 245 875-880, 1987
View abstract

SCRUTTON NS; BERRY A; PERHAM RN PROTEIN ENGINEERING OF GLUTATHIONE-REDUCTASE - OVER-EXPRESSION OF THE GENE FROM ESCHERICHIA-COLI BIOCHEM SOC T 14 1229-1230, 1986

BERRY A; JORDAN PM; SEEHRA JS THE ISOLATION AND CHARACTERIZATION OF CATALYTICALLY COMPETENT PORPHOBILINOGEN DEAMINASE-INTERMEDIATE COMPLEXES FEBS LETT 129 220-224, 1981

JORDAN PM; BERRY A MECHANISM OF ACTION OF PORPHOBILINOGEN DEAMINASE - THE PARTICIPATION OF STABLE ENZYME SUBSTRATE COVALENT INTERMEDIATES BETWEEN PORPHOBILINOGEN AND THE PORPHOBILINOGEN DEAMINASE FROM RHODOPSEUDOMONAS-SPHEROIDES BIOCHEM J 195 177-181, 1981

JORDAN PM; BERRY A PREUROPORPHYRINOGEN, A UNIVERSAL INTERMEDIATE IN THE BIOSYNTHESIS OF UROPORPHYRINOGEN-III FEBS LETT 112 86-88, 1980