Structure and dynamics of mesophilic variants from the homing endonuclease I-DmoI

Josephine Alba; Maria Jose Marcaida; Jesus Prieto; Guillermo Montoya; Rafael Molina; Marco D'Abramo

doi:10.1007/s10822-017-0087-5

Structure and dynamics of mesophilic variants from the homing endonuclease I-DmoI

Josephine Alba, Maria Jose Marcaida, Jesus Prieto, Guillermo Montoya, Rafael Molina, Marco D'Abramo

Protein Structure and Function Program

2 Citations (Scopus)

Abstract

I-DmoI, from the hyperthermophilic archaeon Desulfurococcus mobilis, belongs to the LAGLIDADG homing endonuclease protein family. Its members are highly specific enzymes capable of recognizing long DNA target sequences, thus providing potential tools for genome manipulation. Working towards this particular application, many efforts have been made to generate mesophilic variants of I-DmoI that function at lower temperatures than the wild-type. Here, we report a structural and computational analysis of two I-DmoI mesophilic mutants. Despite very limited structural variations between the crystal structures of these variants and the wild-type, a different dynamical behaviour near the cleavage sites is observed. In particular, both the dynamics of the water molecules and the protein perturbation effect on the cleavage site correlate well with the changes observed in the experimental enzymatic activity.

Original language	English
Journal	Journal of Computer - Aided Molecular Design
Volume	31
Issue number	12
Pages (from-to)	1063-1072
Number of pages	10
ISSN	0920-654X
DOIs	https://doi.org/10.1007/s10822-017-0087-5
Publication status	Published - 1 Dec 2017

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Journal Article

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10.1007/s10822-017-0087-5

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abstract = "I-DmoI, from the hyperthermophilic archaeon Desulfurococcus mobilis, belongs to the LAGLIDADG homing endonuclease protein family. Its members are highly specific enzymes capable of recognizing long DNA target sequences, thus providing potential tools for genome manipulation. Working towards this particular application, many efforts have been made to generate mesophilic variants of I-DmoI that function at lower temperatures than the wild-type. Here, we report a structural and computational analysis of two I-DmoI mesophilic mutants. Despite very limited structural variations between the crystal structures of these variants and the wild-type, a different dynamical behaviour near the cleavage sites is observed. In particular, both the dynamics of the water molecules and the protein perturbation effect on the cleavage site correlate well with the changes observed in the experimental enzymatic activity.",

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T1 - Structure and dynamics of mesophilic variants from the homing endonuclease I-DmoI

AU - Alba, Josephine

AU - Marcaida, Maria Jose

AU - Prieto, Jesus

AU - Montoya, Guillermo

AU - Molina, Rafael

AU - D'Abramo, Marco

PY - 2017/12/1

Y1 - 2017/12/1

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AB - I-DmoI, from the hyperthermophilic archaeon Desulfurococcus mobilis, belongs to the LAGLIDADG homing endonuclease protein family. Its members are highly specific enzymes capable of recognizing long DNA target sequences, thus providing potential tools for genome manipulation. Working towards this particular application, many efforts have been made to generate mesophilic variants of I-DmoI that function at lower temperatures than the wild-type. Here, we report a structural and computational analysis of two I-DmoI mesophilic mutants. Despite very limited structural variations between the crystal structures of these variants and the wild-type, a different dynamical behaviour near the cleavage sites is observed. In particular, both the dynamics of the water molecules and the protein perturbation effect on the cleavage site correlate well with the changes observed in the experimental enzymatic activity.

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Structure and dynamics of mesophilic variants from the homing endonuclease I-DmoI

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