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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Journal of Computer - Aided Molecular Design
Vol/bind	31
Udgave nummer	12
Sider (fra-til)	1063-1072
Antal sider	10
ISSN	0920-654X
DOI	https://doi.org/10.1007/s10822-017-0087-5
Status	Udgivet - 1 dec. 2017

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10.1007/s10822-017-0087-5

Citationsformater

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AU - Alba, Josephine

AU - Marcaida, Maria Jose

AU - Prieto, Jesus

AU - Montoya, Guillermo

AU - Molina, Rafael

AU - D'Abramo, Marco

PY - 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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