D. Drummond, J. Silberg, M. Meyer, C. Wilke, and F. Arnold, On the conservative nature of intragenic recombination, Proceedings of the National Academy of Sciences, vol.102, issue.15, pp.5380-5385, 2005.
DOI : 10.1073/pnas.0500729102

M. Carbone and F. Arnold, Engineering by homologous recombination: exploring sequence and function within a conserved fold, Current Opinion in Structural Biology, vol.17, issue.4, pp.454-459, 2007.
DOI : 10.1016/j.sbi.2007.08.005

O. Maille, P. Bakhtina, M. Tsai, and M. , Structure-based Combinatorial Protein Engineering (SCOPE), Journal of Molecular Biology, vol.321, issue.4, pp.677-691, 2002.
DOI : 10.1016/S0022-2836(02)00675-7

M. Balamurali, D. Sharma, A. Chang, D. Khor, and R. Chu, Recombination of protein fragments: A promising approach toward engineering proteins with novel nanomechanical properties, Protein Science, vol.97, issue.10, pp.1815-1826, 2008.
DOI : 10.1110/ps.036376.108

D. Lemaster and G. Hernandez, Additivity in Both Thermodynamic Stability and Thermal Transition Temperature for Rubredoxin Chimeras via Hybrid Native Partitioning, Structure, vol.13, issue.8, pp.1153-1163, 2005.
DOI : 10.1016/j.str.2005.05.007

P. Heinzelman, C. Snow, I. Wu, C. Nguyen, and A. Villalobos, A family of thermostable fungal cellulases created by structure-guided recombination, Proceedings of the National Academy of Sciences, vol.106, issue.14, pp.5610-5615, 2009.
DOI : 10.1073/pnas.0901417106

C. Otey, J. Silberg, C. Voigt, J. Endelman, and G. Bandara, Functional Evolution and Structural Conservation in Chimeric Cytochromes P450, Chemistry & Biology, vol.11, issue.3, pp.309-318, 2004.
DOI : 10.1016/j.chembiol.2004.02.018

P. Heinzelman, C. Snow, M. Smith, X. Yu, and A. Kannan, SCHEMA Recombination of a Fungal Cellulase Uncovers a Single Mutation That Contributes Markedly to Stability, Journal of Biological Chemistry, vol.284, issue.39, pp.26229-26233, 2009.
DOI : 10.1074/jbc.C109.034058

C. Voigt, C. Martinez, Z. Wang, S. Mayo, and F. Arnold, Protein building blocks preserved by recombination, Nature Structural Biology, vol.9, pp.553-558, 2002.
DOI : 10.1038/nsb805

M. Meyer, L. Hochrein, and F. Arnold, Structure-guided SCHEMA recombination of distantly related ??-lactamases, Protein Engineering Design and Selection, vol.19, issue.12, pp.563-570, 2006.
DOI : 10.1093/protein/gzl045

K. Bush, Bench-to-bedside review: The role of ??-lactamases in antibiotic-resistant Gram-negative infections, Critical Care, vol.14, issue.3, pp.224-224, 2010.
DOI : 10.1186/cc8892

K. Hiraga and F. Arnold, General Method for Sequence-independent Site-directed Chimeragenesis, Journal of Molecular Biology, vol.330, issue.2, pp.287-296, 2003.
DOI : 10.1016/S0022-2836(03)00590-4

M. Meyer, J. Silberg, C. Voigt, J. Endelman, and S. Mayo, Library analysis of SCHEMA-guided protein recombination, Protein Science, vol.16, issue.8, pp.1686-1693, 2003.
DOI : 10.1110/ps.0306603

G. Bhabha, J. Lee, D. Ekiert, J. Gam, and I. Wilson, A Dynamic Knockout Reveals That Conformational Fluctuations Influence the Chemical Step of Enzyme Catalysis, Science, vol.332, issue.6026, pp.234-238, 2011.
DOI : 10.1126/science.1198542

N. Doucet and J. Pelletier, Gaining Insight into Enzyme Function through Correlation with Protein Motions, In: Protein Engineering, vol.16, pp.187-211, 2009.
DOI : 10.1002/9783527634026.ch7

M. Carroll, R. Mauldin, A. Gromova, S. Singleton, and E. Collins, Evidence for dynamics in proteins as a mechanism for ligand dissociation, Nature Chemical Biology, vol.21, issue.3, pp.246-252, 2012.
DOI : 10.1021/bi00387a052

A. Tousignant and J. Pelletier, Protein Motions Promote Catalysis, Chemistry & Biology, vol.11, issue.8, pp.1037-1042, 2004.
DOI : 10.1016/j.chembiol.2004.06.007

B. Ma and R. Nussinov, Enzyme dynamics point to stepwise conformational selection in catalysis, Current Opinion in Chemical Biology, vol.14, issue.5, pp.652-659, 2010.
DOI : 10.1016/j.cbpa.2010.08.012

Z. Nagel and J. Klinman, Corrigendum: A 21st century revisionist's view at a turning point in enzymology, Nature Chemical Biology, vol.5, issue.9, pp.696-696, 2009.
DOI : 10.1038/nchembio0909-696c

K. Henzler-wildman and D. Kern, Dynamic personalities of proteins, Nature, vol.124, issue.7172, pp.964-972, 2007.
DOI : 10.1038/nature06522

C. Jelsch, L. Mourey, J. Masson, and J. Samama, Crystal structure ofEscherichia coli TEM1 ??-lactamase at 1.8 ?? resolution, Proteins: Structure, Function, and Genetics, vol.257, issue.4, pp.364-383, 1993.
DOI : 10.1002/prot.340160406

S. Morin and S. Gagné, NMR Dynamics of PSE-4 ??-Lactamase: An Interplay of ps-ns Order and ??s-ms Motions in the Active Site, Biophysical Journal, vol.96, issue.11, pp.4681-4691, 2009.
DOI : 10.1016/j.bpj.2009.02.068

O. Fisette, S. Morin, P. Savard, P. Lagüe, and S. Gagné, TEM-1 Backbone Dynamics???Insights from Combined Molecular Dynamics and Nuclear Magnetic Resonance, Biophysical Journal, vol.98, issue.4, pp.637-645, 2010.
DOI : 10.1016/j.bpj.2009.08.061

S. Morin, C. Clouthier, S. Gobeil, J. Pelletier, and S. Gagné, Backbone resonance assignments of an artificially engineered TEM-1/PSE-4 Class A ??-lactamase chimera, Biomolecular NMR Assignments, vol.4, issue.Pt 1, pp.127-130, 2010.
DOI : 10.1007/s12104-010-9227-8

C. Bebrone, C. Moali, F. Mahy, S. Rival, and J. Docquier, CENTA as a Chromogenic Substrate for Studying ??-Lactamases, Antimicrobial Agents and Chemotherapy, vol.45, issue.6, pp.1868-1871, 2001.
DOI : 10.1128/AAC.45.6.1868-1871.2001

URL : https://hal.archives-ouvertes.fr/hal-00313147

A. Sosa-peinado, D. Mustafi, and M. Makinen, Overexpression and biosynthetic deuterium enrichment of TEM-1 beta-lactamase for structural characterization by magnetic resonance methods, pp.235-245, 2000.

N. Doucet, P. Savard, J. Pelletier, and S. Gagné, NMR Investigation of Tyr105 Mutants in TEM-1 beta-Lactamase: DYNAMICS ARE CORRELATED WITH FUNCTION, Journal of Biological Chemistry, vol.282, issue.29, pp.21448-21459, 2007.
DOI : 10.1074/jbc.M609777200

URL : https://hal.archives-ouvertes.fr/pasteur-00736958

O. Bolduc, C. Clouthier, J. Pelletier, and J. Masson, Peptide Self-Assembled Monolayers for Label-Free and Unamplified Surface Plasmon Resonance Biosensing in Crude Cell Lysate, Analytical Chemistry, vol.81, issue.16, pp.6779-6788, 2009.
DOI : 10.1021/ac900956y

D. Wals, P. Doucet, N. Pelletier, and J. , High tolerance to simultaneous active-site mutations in TEM-1 beta-lactamase: Distinct mutational paths provide more generalized beta-lactam recognition, Protein Sci, vol.18, pp.147-160, 2009.

A. Savitzky and M. Golay, Smoothing and Differentiation of Data by Simplified Least Squares Procedures., Analytical Chemistry, vol.36, issue.8, pp.1627-1639, 1964.
DOI : 10.1021/ac60214a047

F. Niesen, H. Berglund, and M. Vedadi, The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability, Nature Protocols, vol.4, issue.9, pp.2212-2221, 2007.
DOI : 10.1038/nprot.2006.202

A. Bouthors, N. Dagoneau-blanchard, T. Naas, P. Nordmann, and V. Jarlier, Role of residues 104, 164, 166, 238 and 240 in the substrate profile of PER-1 ??-lactamase hydrolysing third-generation cephalosporins, Biochemical Journal, vol.330, issue.3, pp.1443-1449, 1998.
DOI : 10.1042/bj3301443

C. Tribuddharat, R. Moore, P. Baker, and D. Woods, Burkholderia pseudomallei Class A ??-Lactamase Mutations That Confer Selective Resistance against Ceftazidime or Clavulanic Acid Inhibition, Antimicrobial Agents and Chemotherapy, vol.47, issue.7, pp.2082-2087, 2003.
DOI : 10.1128/AAC.47.7.2082-2087.2003

C. Cantu and T. Palzkill, The Role of Residue 238 of TEM-1 ??-Lactamase in the Hydrolysis of Extended-spectrum Antibiotics, Journal of Biological Chemistry, vol.273, issue.41, pp.26603-26609, 1998.
DOI : 10.1074/jbc.273.41.26603

N. Farrow, R. Muhandiram, A. Singer, S. Pascal, and C. Kay, Backbone Dynamics of a Free and a Phosphopeptide-Complexed Src Homology 2 Domain Studied by 15N NMR Relaxation, Biochemistry, vol.33, issue.19, pp.5984-6003, 1994.
DOI : 10.1021/bi00185a040

G. Zhu, Y. Xia, L. Nicholson, and K. Sze, Protein Dynamics Measurements by TROSY-Based NMR Experiments, Journal of Magnetic Resonance, vol.143, issue.2, pp.423-426, 2000.
DOI : 10.1006/jmre.2000.2022

F. Delaglio, S. Grzesiek, G. Vuister, G. Zhu, and J. Pfeifer, NMRPipe: A multidimensional spectral processing system based on UNIX pipes, Journal of Biomolecular NMR, vol.6, issue.3, pp.277-293, 1995.
DOI : 10.1007/BF00197809

B. Johnson and R. Blevins, NMR View: A computer program for the visualization and analysis of NMR data, Journal of Biomolecular NMR, vol.88, issue.5, pp.603-614, 1994.
DOI : 10.1007/BF00404272

E. Auvergne and P. Gooley, Optimisation of NMR dynamic models II. A new methodology for the dual optimisation of the model-free parameters and the Brownian rotational diffusion tensor, Journal of Biomolecular NMR, vol.44, issue.1, pp.121-133, 2008.
DOI : 10.1007/s10858-007-9213-3

E. Auvergne and P. Gooley, Optimisation of NMR dynamic models I. Minimisation algorithms and their performance within the model-free and Brownian rotational diffusion spaces, Journal of Biomolecular NMR, vol.342, issue.5, pp.107-119, 2008.
DOI : 10.1007/s10858-007-9214-2

S. Morin and S. Gagné, Simple tests for the validation of multiple field spin relaxation data, Journal of Biomolecular NMR, vol.342, issue.5, pp.361-372, 2009.
DOI : 10.1007/s10858-009-9381-4

E. Auvergne and P. Gooley, The use of model selection in the model-free analysis of protein dynamics, Journal of Biomolecular NMR, vol.25, issue.1, pp.25-39, 2003.
DOI : 10.1023/A:1021902006114

E. Auvergne and P. Gooley, Model-free model elimination: A new step in the model-free dynamic analysis of NMR relaxation data, Journal of Biomolecular NMR, vol.342, issue.2, pp.117-135, 2006.
DOI : 10.1007/s10858-006-9007-z

W. Kabsch and C. Sander, Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features, Biopolymers, vol.33, issue.12, pp.2577-2637, 1983.
DOI : 10.1002/bip.360221211

H. Akaike, Information theory and an extension of the maximum likelihood principle, Petrov BN, Csaki F, 1973.

B. Stec, K. Holtz, C. Wojciechowski, and E. Kantrowitz, Structure of the wild-type TEM-1 ??-lactamase at 1.55????? and the mutant enzyme Ser70Ala at 2.1????? suggest the mode of noncovalent catalysis for the mutant enzyme, Acta Crystallographica Section D Biological Crystallography, vol.61, issue.8, pp.1072-1079, 2005.
DOI : 10.1107/S0907444905014356

X. Wang, G. Minasov, and B. Shoichet, Noncovalent interaction energies in covalent complexes: TEM-1 ?-lactamase and ?-lactams, Proteins: Structure, Function, and Genetics, vol.273, issue.1, pp.86-96, 2002.
DOI : 10.1002/prot.10058

A. Savoie, F. Sanschagrin, T. Palzkill, N. Voyer, and R. Levesque, Structure-function analysis of ??-helix H4 using PSE-4 as a model enzyme representative of class A ??-lactamases, Protein Engineering Design and Selection, vol.13, issue.4, pp.267-274, 2000.
DOI : 10.1093/protein/13.4.267

C. Layton and H. Hellinga, Thermodynamic Analysis of Ligand-Induced Changes in Protein Thermal Unfolding Applied to High-Throughput Determination of Ligand Affinities with Extrinsic Fluorescent Dyes, Biochemistry, vol.49, issue.51, pp.10831-10841, 2010.
DOI : 10.1021/bi101414z

W. Huang, J. Petrosino, M. Hirsch, P. Shenkin, and T. Palzkill, Amino Acid Sequence Determinants of ??-Lactamase Structure and Activity, Journal of Molecular Biology, vol.258, issue.4, pp.688-703, 1996.
DOI : 10.1006/jmbi.1996.0279

S. Morin, R. Levesque, and S. Gagné, Letter to the Editor, Journal of Biomolecular NMR, vol.40, issue.S1, p.11, 2006.
DOI : 10.1007/s10858-005-5343-7

N. Farrow, O. Zhang, A. Szabo, D. Torchia, and L. Kay, Spectral density function mapping using 15 N relaxation data exclusively, J Biomol NMR, vol.6, pp.153-162, 1995.

G. Lipari and A. Szabo, Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity, Journal of the American Chemical Society, vol.104, issue.17, pp.4546-4559, 1982.
DOI : 10.1021/ja00381a009

G. Lipari and A. Szabo, Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 2. Analysis of experimental results, Journal of the American Chemical Society, vol.104, issue.17, pp.4559-4570, 1982.
DOI : 10.1021/ja00381a010

G. Lipari and A. Szabo, Analysis of NMRrelaxation data on macromolecules using the model-free approach, Biophys J, vol.37, pp.380-380, 1982.

S. Morin, A practical guide to protein dynamics from 15N spin relaxation in solution, Progress in Nuclear Magnetic Resonance Spectroscopy, vol.59, issue.3, pp.245-262, 2011.
DOI : 10.1016/j.pnmrs.2010.12.003

N. Doucet, D. Wals, P. Pelletier, and J. , Site-saturation Mutagenesis of Tyr-105 Reveals Its Importance in Substrate Stabilization and Discrimination in TEM-1 ??-Lactamase, Journal of Biological Chemistry, vol.279, issue.44, pp.46295-46303, 2004.
DOI : 10.1074/jbc.M407606200

URL : https://hal.archives-ouvertes.fr/pasteur-00736939

N. Doucet and J. Pelletier, Simulated annealing exploration of an active-site tyrosine in TEM-1??-lactamase suggests the existence of alternate conformations, Proteins: Structure, Function, and Bioinformatics, vol.48, issue.2, pp.340-348, 2007.
DOI : 10.1002/prot.21485

URL : https://hal.archives-ouvertes.fr/pasteur-00736957

F. Bos and J. Pleiss, Multiple Molecular Dynamics Simulations of TEM ??-Lactamase: Dynamics and Water Binding of the ??-Loop, Biophysical Journal, vol.97, issue.9, pp.2550-2558, 2009.
DOI : 10.1016/j.bpj.2009.08.031

D. Roccatano, G. Sbardella, M. Aschi, G. Amicosante, and C. Bossa, Dynamical Aspects of TEM-1 ??-Lactamase Probed by Molecular Dynamics, Journal of Computer-Aided Molecular Design, vol.103, issue.5, pp.329-340, 2005.
DOI : 10.1007/s10822-005-7003-0

R. Ambler, A. Coulson, J. Frère, J. Ghuysen, and B. Joris, -lactamases, Biochemical Journal, vol.276, issue.1, pp.269-270, 1991.
DOI : 10.1042/bj2760269

URL : https://hal.archives-ouvertes.fr/inserm-00423741