Journal
MOLECULAR BIOLOGY AND EVOLUTION
Volume 40, Issue 5, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/molbev/msad099
Keywords
enzyme cold adaptation; lactate dehydrogenase; computer simulation
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Computer simulations are used to study the cold adaptation of lactate dehydrogenases from Antarctic and sub-Antarctic fish species. The results show that these enzymes have lower activation enthalpy and more negative entropy, which is a common feature of psychrophilic enzymes. The simulations also explain the differences in thermal stability and substrate binding affinity between the two cold-adapted enzymes.
Cold-adapted enzymes from psychrophilic and psychrotolerant species are characterized by a higher catalytic activity at low temperature than their mesophilic orthologs and are also usually found to be more thermolabile. Computer simulations of the catalytic reactions have been shown to be a very powerful tool for analyzing the structural and energetic origins of these effects. Here, we examine the cold adaptation of lactate dehydrogenases from two Antarctic and sub-Antarctic fish species using this approach and compare our results with those obtained for the orthologous dogfish enzyme. Direct calculations of thermodynamic activation parameters show that the cold-adapted fish enzymes are characterized by a lower activation enthalpy and a more negative entropy term. This appears to be a universal feature of psychrophilic enzymes, and it is found to originate from a higher flexibility of certain parts of the protein surface. We also carry out free energy simulations that address the differences in thermal stability and substrate binding affinity between the two cold-adapted enzymes, which only differ by a single mutation. These calculations capture the effects previously seen in in vitro studies and provide straightforward explanations of these experimental results.
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