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Computation of enzyme cold adaptation

Nature Reviews Chemistry volume 1, Article number: 0051 (2017) Cite this article

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Abstract

Earth has several environments that are potentially hostile to life. The survival of organisms has required the expression of proteins that are adapted to function under extreme temperature, pH, pressure or ionic strength. However, the origin of such adaptations remains, in most cases, an open question. This Review presents a detailed analysis of the specialized enzymes that are able to maintain high catalytic rates at low temperatures and highlights the important role that computational studies have in uncovering the evolutionary principles behind the cold adaptation of enzymes. Although often highly homologous to their mesophilic counterparts, these cold-adapted enzymes have characteristic and universal properties that reflect their evolutionary optimization. In addition to exhibiting maximum reaction rates at lower temperatures, cold-adapted enzymes are more heat-labile and their catalytic mechanisms have distinct signatures in terms of the thermodynamic activation parameters. The structural origins of these properties have been elusive but are hypothesized to be related to protein flexibility.

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Figure 1: Characteristics of warm- and cold-adapted enzymes.
Figure 2: Protein flexibility and computer simulations of cold- and warm-adapted enzyme reactions.
Figure 3: Effect of protein surface restraints on the thermodynamic activation parameters.
Figure 4: A psychrophilic ribosome.

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References

  1. van den Burg, B. Extremophiles as a source for novel enzymes. Curr. Opin. Microbiol. 6, 213–218 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Gomes, J. & Steiner, W. The biocatalytic potential of extremophiles and extremozymes. Food Technol. Biotechnol. 42, 223–235 (2004).

    CAS  Google Scholar 

  3. Hough, D. W. & Danson, M. J. Extremozymes. Curr. Opin. Chem. Biol. 3, 39–46 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. Danson, M. J. & Hough, D. W. The structural basis of protein halophilicity. Comp. Biochem. Physiol. A 117, 307–312 (1997).

    Article  Google Scholar 

  5. Madern, D., Ebel, C. & Zaccai, G. Halophilic adaptation of enzymes. Extremophiles 4, 91–98 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Gros, M. & Jaenicke, R. Proteins under pressure. Eur. J. Biochem. 221, 617–630 (1994).

    Article  Google Scholar 

  7. Daniel, I., Oger, P. & Winter, R. Origins of life and biochemistry under high-pressure conditions. Chem. Soc. Rev. 35, 858–875 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Lauro, F. M., Chastain, R. A., Blankenship, L. E., Yayanos, A. A. & Bartlett, D. H. The unique 16S rRNA genes of piezophiles reflect both phylogeny and adaptation. Appl. Environ. Microbiol. 73, 838–845 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Stetter, K. O. Extremophiles and their adaptation to hot environments. FEBS Lett. 452, 22–25 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Hurst, L. D. & Merchant, A. R. High guanine–cytosine content is not an adaptation to high temperature: a comparative analysis amongst prokaryotes. Proc. R. Soc. Lond. B 268, 493–497 (2000).

    Article  Google Scholar 

  11. Nakashima, H., Fukuchi, S. & Nishikawa, K. Compositional changes in RNA, DNA and proteins for bacterial adaptation to higher and lower temperatures. J. Biochem. 133, 507–513 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Khachane, A. N., Timmis, K. N. & Martins dos Santos, V. A. P. Uracil content of 16S rRNA of thermophilic and psychrophilic prokaryotes correlates inversely with their optimal growth temperatures. Nucl. Acids Res. 33, 4016–4022 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Feller, G. & Gerday, C. Psychrophilic enzymes: hot topics in cold adadptation. Nat. Rev. Microbiol. 1, 200–208 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. D’Amico, S., Marx, J. C., Gerday, C. & Feller, G. Activity–stability relationships in extremophilic enzymes. J. Biol. Chem. 278, 7891–7896 (2003).

    Article  PubMed  CAS  Google Scholar 

  15. Dias, C. L. et al. The hydrophobic effect and its role in cold denaturation. Cryobiology 60, 91–99 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Sicheri, F. & Yang, D. S. C. Ice-binding structure and mechanism of an antifreeze protein from winter flounder. Nature 375, 427–431 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Yeh, Y. & Feeney, R. E. Antifreeze proteins: structures and mechanisms of function. Chem. Rev. 96, 601–617 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Jaenicke, R. & Böhm, G. The stability of proteins in extreme environments. Curr. Opin. Struct. Biol. 8, 738–748 (1998).

    Article  CAS  PubMed  Google Scholar 

  19. Kumar, S. & Nussinov, R. How do thermophilic proteins deal with heat? Cell. Mol. Life Sci. 58, 1216–1233 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Vieille, C. & Zeikus, G. J. Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for thermostability. Microbiol. Mol. Biol. Rev. 65, 1–43 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Berezovsky, I. N. & Shakhnovich, E. I. Physics and evolution of thermophilic adaptation. Proc. Natl Acad. Sci. USA 102, 12742–12747 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lazaridis, T., Lee, I. & Karplus, M. Dynamics and unfolding pathways of a hyperthermophilic and a mesophilic rubredoxin. Protein Sci. 6, 2589–2605 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kovacic, F., Mandrysch, A., Poojari, C., Strodel, B. & Jaeger, K. E. Structural features determining thermal adaptation of esterases. Protein Eng. Des. Sel. 29, 65–76 (2016).

    Article  CAS  PubMed  Google Scholar 

  24. Dominy, B. N., Minoux, H. & Brooks, C. L. III . An electrostatic basis for the stability of thermophilic proteins. Proteins 57, 128–141 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Missimer, J. H. et al. Configurational entropy elucidates the role of salt-bridge networks in protein thermostability. Protein Sci. 16, 1349–1359 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Roca, M., Liu, H., Messer, B. & Warshel, A. On the relationship between thermal stability and catalytic power of enzymes. Biochemistry 46, 15067–15088 (2007).

    Article  CAS  Google Scholar 

  27. Bjelic, S., Brandsdal, B. O. & Åqvist, J. Cold adaptation of enzyme reaction rates. Biochemistry 47, 10049–10057 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Isaksen, G. V., Åqvist, J. & Brandsdal, B. O. Protein surface softness is the origin of enzyme cold-adaptation of trypsin. PLoS Comput. Biol. 8, e1003813 (2014).

    Article  CAS  Google Scholar 

  29. Isaksen, G. V., Åqvist, J. & Brandsdal, B. O. Enzyme surface rigidity tunes the temperature dependence of catalytic rates. Proc. Natl Acad. Sci. USA 113, 7822–7827 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Åqvist, J., Wennerström, P., Nervall, M., Bjelic, S. & Brandsdal, B. O. Molecular dynamics simulations of water and biomolecules with a Monte Carlo constant pressure algorithm. Chem. Phys. Lett. 384, 288–294 (2004).

    Article  CAS  Google Scholar 

  31. Kitchen, D. B., Reed, L. H. & Levy, R. M. Molecular dynamics simulation of solvated protein at high pressure. Biochemistry 31, 10083–10093 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Paci, E. High pressure simulations of biomolecules. Biochim. Biophys. Acta 1595, 185–200 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Low, P. S., Bada, J. L. & Somero, G. N. Temperature adaptation of enzymes: roles of the free energy, the enthalpy and the entropy of activation. Proc. Natl Acad. Sci. USA 70, 430–432 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lonhienne, T., Gerday, C. & Feller, G. Psychrophilic enzymes: revisiting the thermodynamic parameters of activation may explain local flexibility. Biochim. Biophys. Acta 1543, 1–10 (2000).

    Article  CAS  PubMed  Google Scholar 

  35. Siddiqui, K. S. & Cavicchioli, R. Cold-adapted enzymes. Annu. Rev. Biochem. 75, 403–433 (2006).

    Article  CAS  PubMed  Google Scholar 

  36. Fields, P. A. & Somero, G. N. Hot spots in cold adaptation: localized increases in conformational flexibility in lactate dehydrogenase A4 orthologs of Antarctic notothenoid fishes. Proc. Natl Acad. Sci. USA 95, 11476–11481 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Altermark, B., Niiranen, L., Willasen, N. P., Smalås, A. O. & Moe, E. Comparative studies of endonuclease I from cold-adapted Vibrio salmonicida and mesophilic Vibrio cholerae. FEBS J. 274, 252–263 (2007).

    Article  CAS  PubMed  Google Scholar 

  38. Liang, Z. X., Tsigos, I., Bouriotis, V. & Klinman, J. P. Impact of protein flexibility on hydride-transfer parameters in thermophilic and psychrophilic alcohol dehydrogenases. J. Am. Chem. Soc. 126, 9500–9501 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. Daniel, R. M. & Danson, M. J. A new understanding of how temperature affects the catalytic activity of enzymes. Trends Biochem. Sci. 35, 584–591 (2010).

    Article  CAS  PubMed  Google Scholar 

  40. Hobbs, J. K. et al. Change in heat capacity for enzyme catalysis determines temperature dependence of enzyme catalyzed rates. ACS Chem. Biol. 8, 2388–2393 (2008).

    Article  CAS  Google Scholar 

  41. Arcus, V. L. Prentice, E. J. et al. On the temperature dependence of enzyme-catalyzed rates. Biochemistry 55, 1681–1688 (2016).

    Article  CAS  PubMed  Google Scholar 

  42. Nguyen, V. et al. Evolutionary drivers of thermoadaptation in enzyme catalysis. Science 355, 289–294 (2017).

    Article  CAS  PubMed  Google Scholar 

  43. Elias, M., Wieczorek, G., Rosenne, S. & Tawfik, D. S. The universality of enzymatic rate–temperature dependency. Trends Biochem. Sci. 39, 1–7 (2014).

    Article  CAS  PubMed  Google Scholar 

  44. Petrescu, I. et al. Xylanase from the psychrophilic yeast Cryptococcus adeliae. Extremophiles 4, 137–144 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Smalås, A. O., Heimstad, E. S., Hordvik, A., Willasen, W. P. & Male, R. Cold adaptation of enzymes: structural comparison between salmon and bovine trypsins. Proteins 20, 149–166 (1994).

    Article  PubMed  Google Scholar 

  46. Olufsen, M., Smalås, A. O., Moe, E. & Brandsdal, B. Increased flexibility as a strategy for cold adpatation. J. Biol. Chem. 280, 18042–18048 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Papaleo, E., Riccardi, L., Villa, C., Fantucci, P. & De Gioia, L. Flexibility and enzymatic cold-adaptation: a comparative molecular dynamics investigation of the elastase family. Biochim. Biophys. Acta 1764, 1397–1406 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Papaleo, E. et al. Protein flexibility in psychrophilic and mesophilic trypsins. Evidence of evolutionary conservation of protein dynamics in trypsin-like serine-proteases. FEBS Lett. 582, 1008–1018 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Åqvist, J., Kazemi, M., Isaksen, G. V. & Brandsdal, B. O. Entropy and enzyme catalysis. Acc. Chem. Res. 50, 199–207 (2017).

    Article  PubMed  CAS  Google Scholar 

  50. Kazemi, M. & Åqvist, J. Chemical reaction mechanisms in solution from brute force computational Arrhenius plots. Nat. Commun. 6, 7293 (2015).

    Article  CAS  PubMed  Google Scholar 

  51. Kazemi, M., Himo, F. & Åqvist, J. Enzyme catalysis by entropy without Circe effect. Proc. Natl Acad. Sci. USA 113, 2406–2411 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Åqvist, J. & Kamerlin, S. C. L. Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome. Sci. Rep. 5, 15817 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Åqvist, J. & Kamerlin, S. C. L. Conserved motifs in different classes of GTPases dictate their specific modes of catalysis. ACS Catal. 6, 1737–1743 (2016).

    Article  CAS  Google Scholar 

  54. Warshel, A. Computer Modeling of Chemical Reactions in Enzymes and Solutions (Wiley, 1991).

    Google Scholar 

  55. Åqvist, J. & Warshel, A. Simulation of enzyme reactions using valence bond force fields and other hybrid quantum/classical approaches. Chem. Rev. 93, 2523–2544 (1993).

    Article  Google Scholar 

  56. Snider, M. J., Gaunitz, S., Ridgway, C., Short, S. A. & Wolfenden, R. Temperature effects on the catalytic efficiency, rate enhancement, and transition state affinity of cytidine deaminase, and the thermodynamic consequences for catalysis of removing a substrate “anchor”. Biochemistry 39, 9746–9753 (2000).

    Article  CAS  PubMed  Google Scholar 

  57. Outzen, H., Berglund, G. I., Smalås, A. O. & Willasen, N. P. Temperature and pH sensitivity of trypsins from Atlantic salmon (Salmo salar) in comparison with bovine and porcine trypsin. Comp. Biochem. Physiol. B 115, 33–45 (1996).

    Article  CAS  PubMed  Google Scholar 

  58. Ghanem, M., Li, L., Wing, C. & Schramm, V. L. Altered thermodynamics from remote mutations altering human toward bovine purine nucleoside phosphorylase. Biochemistry 47, 2559–2564 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Isaksen, G. V., Åqvist, J. & Brandsdal, B. O. Thermodynamics of the purine nucleoside phosphorylase reaction revealed by computer simulations. Biochemistry 56, 306–312 (2017).

    Article  CAS  PubMed  Google Scholar 

  60. Leiros, H. K. S., McSweeney, S. M. & Smalås, A. O. Atomic resolution structures of trypsin provide insight into structural radiation damage. Acta Crystallogr. D 57, 488–497 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Liebschner, D., Dauter, M., Brzuszkiewicz, A. & Dauter, Z. On the reproducibility of protein crystal structures: five atomic resolution structures of trypsin. Acta Crystallogr. D 69, 1447–1462 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bellissent-Funel, M. C. et al. Water determines the structure and dynamics of proteins. Chem. Rev. 116, 7673–7697 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pucci, F. & Rooman, M. Physical and molecular bases of protein thermal stability and cold-adaptation. Curr. Opin. Struct. Biol. 42, 117–128 (2017).

    Article  CAS  PubMed  Google Scholar 

  64. Rodriguez-Correa, D. & Dahlberg, A. E. Kinetic and thermodynamic studies of of peptidyltransferase in ribosomes from the extreme thermophile Thermus thermophilus. RNA 14, 2314–2318 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Siddiqui, K. S., Cavicchioli, R. & Thomas, T. Thermodynamic activation parameters of elongation factor 2 (EF-2) proteins from psychrotolerant and thermophilic Archaea. Extremophiles 6, 143–150 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Merlino, A. et al. Structure and flexibility in cold-adapted iron superoxide dismutases: the case of the enzyme isolated from Pseudoalteromonas haloplanktis. J. Struct. Biol. 172, 343–352 (2010).

    Article  CAS  PubMed  Google Scholar 

  67. Struvay, C. & Feller, G. Optimization to low temperature activity in psychrophilic enzymes. Int. J. Mol. Sci. 13, 11643–11665 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Harms, M. J. & Thornton, J. W. Evolutionary biochemistry: revealing the historical and physical causes of protein properties. Nat. Rev. Genet. 14, 559–571 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shoichet, B. K., Baase, W. A., Kuroki, R. & Matthews, B. W. A relationship between protein stability and protein function. Proc. Natl Acad. Sci. USA 92, 452–456 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Dang, L. X., Merz Jr, K. M. & Kollman, P. A. Free energy calculations on protein stability: Thr-157 → Val-157 mutation of T4 lysozyme. J. Am. Chem. Soc. 111, 8505–8508 (1989).

    Article  CAS  Google Scholar 

  71. Pan, Y. P. & Daggett, V. Direct comparison of experimental and calculated folding free energies for hydrophobic deletion mutants of chymotrypsin inhibitor 2. Biochemistry 40, 2723–2731 (2001).

    Article  CAS  PubMed  Google Scholar 

  72. Seeliger, D. & de Groot, B. L. Protein thermostability calculations using alchemical free energy simulations. Biophys. J. 98, 2309–2316 (2011).

    Article  CAS  Google Scholar 

  73. Folch, B., Dehouck, Y. & Rooman, M. Thermo- and mesostabilizing protein interactions identified by temperature-dependent statistical potentials. Biophys. J. 98, 667–677 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Pucci, F., Bourgeas, R. & Rooman, M. Predicting protein thermal stability changes upon point mutations using statistical potentials: introducing HoTMuSiC. Sci. Rep. 6, 23257 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Eyring, H. The activated complex in chemical reactions. J. Chem. Phys. 3, 107–115 (1935).

    Article  CAS  Google Scholar 

  76. Evans, M. G. & Polanyi, M. Some applications of the transition state method to the calculation of reaction velocities, especially in solution. Trans. Faraday Soc. 31, 875–893 (1935).

    Article  CAS  Google Scholar 

  77. Bjelic, S. & Åqvist, J. Catalysis and linear free energy relationships in aspartic proteases. Biochemistry 45, 7709–7723 (2006).

    Article  CAS  PubMed  Google Scholar 

  78. Russell, R. J., Ferguson, J. M., Hough, D. W., Danson, M. J. & Taylor, G. L. The crystal structure of citrate synthase from the hyperthermophilic archaeon Pyrococcus furiosus at 1.9 Å resolution. Biochemistry 36, 9983–9994 (1997).

    Article  CAS  PubMed  Google Scholar 

  79. Russell, R. J., Gerike, U., Danson, M. J., Hough, D. W. & Taylor, G. L. Structural adaptations of the cold-active citrate synthase from an Antarctic bacterium. Structure 6, 351—361 (1998).

    Article  CAS  PubMed  Google Scholar 

  80. Leiros, H. K. S., Willassen, N. P. & Smalås, A. O. Structural comparison of psychrophilic and mesophilic trypsins: elucidating the molecular basis of cold-adaptation. Eur. J. Biochem. 267, 1039–1049 (2000).

    Article  CAS  PubMed  Google Scholar 

  81. Mereghetti, P. et al. Near native-state conformational landscape of psychrophilic and mesophilic enzymes: probing the folding funnel model. J. Phys. Chem. B. 114, 7609–7619 (2010).

    Article  CAS  PubMed  Google Scholar 

  82. Olufsen, M., Brandsdal, B. O. & Smalås, A. O. Comparative unfolding studies of psychrophilic and mesophilic uracil DNA glycosylase: MD simulations show reduced thermal stability of the cold-adapted enzyme. J. Mol. Graph. Model. 26, 124–134 (2007).

    Article  CAS  PubMed  Google Scholar 

  83. Papaleo, E., Olufsen, M., De Gioia, L. & Brandsdal, B. O. Optimization of electrostatics as a strategy for cold-adaptation: a case study of cold- and warm-active elastases. J. Mol. Graph. Model. 26, 93–103 (2007).

    Article  CAS  PubMed  Google Scholar 

  84. Michetti, D. et al. A comparative study of cold- and warm-adapted Endonucleases A using sequence analyses and molecular dynamics simulations. PLoS ONE 12, e0169586 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Papaleo, E., Pasi, M., Tiberti, M. & De Gioia, L. Molecular dynamics of mesophilic-like mutants of a cold-adapted enzyme: insights into distal effects induced by the mutations. PLoS ONE 6, e24214 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zanphorlin, L. M. et al. Oligomerization as a strategy for cold adaptation: structure and dynamics of the GH1 β-glucosidase from Exiguobacterium antarcticum B7. Sci. Rep. 6, 23776 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Parvizpour, S., Razmara, J., Ramli, A. N. M., Md Illias, R. & Shamsir, M. S. Structural and functional analysis of a novel psychrophilic β-mannanase from Glaciozyma antarctica PI12. J. Comput. Aided Mol. Des. 28, 685–698 (2014).

    Article  CAS  PubMed  Google Scholar 

  88. Kim, M. K. et al. Structure-based investigation into the functional roles of the extended loop and substrate-recognition sites in an endo-β-1,4-d-mannanase from the Antarctic springtail. Cryptopygus antarcticus. Proteins 82, 3217–3223 (2014).

    Article  CAS  PubMed  Google Scholar 

  89. Gatti-Lafranconi, P. et al. Evolution of stability in a cold-active enzyme elicits specificity relaxation and highlights substrate-related effects on temperature adaptation. J. Mol. Biol. 395, 155–166 (2010).

    Article  CAS  PubMed  Google Scholar 

  90. Sigtryggsdóttir, Á. R., Papaleo, E., Thorbjarnardóttir, S. H. & Kristjánsson, M. M. Flexibility of cold- and heat-adapted subtilisin-like serine proteinases evaluated with fluorescence quenching and molecular dynamics. Biochim. Biophys. Acta 1844, 705–712 (2014).

    Article  PubMed  CAS  Google Scholar 

  91. Xie, B. B. et al. Cold adaptation of zinc metalloproteases in the thermolysin family from deep sea and arctic sea ice bacteria revealed by catalytic and structural properties and molecular dynamics: new insights into relationship between conformational flexibility and hydrogen bonding. J. Biol. Chem. 284, 9257–9269 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Adekoya, O. A., Helland, R., Willassen, N. P. & Sylte, I. Comparative sequence and structure analysis reveal features of cold adaptation of an enzyme in the thermolysin family. Proteins 62, 435–449 (2006).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge support from the Swedish Research Council (VR), the Knut and Alice Wallenberg Foundation and the Research Council of Norway (through a Centre of Excellence grant, 179568/V30).

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  1. Department of Cell and Molecular Biology, Uppsala University, Biomedical Centre, Box 596, Uppsala, SE-751 24, Sweden

    Johan Åqvist & Geir Villy Isaksen

  2. Department of Chemistry, The Centre for Theoretical and Computational Chemistry, University of Tromsø, Tromsø, N-9037, Norway

    Geir Villy Isaksen & Bjørn Olav Brandsdal

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Åqvist, J., Isaksen, G. & Brandsdal, B. Computation of enzyme cold adaptation. Nat Rev Chem 1, 0051 (2017). https://doi.org/10.1038/s41570-017-0051

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