On the structural affinity of macromolecules with different biological properties: Molecular dynamics simulations of a series of TEM-1 mutants
Abstract
Highlights: •We have performed molecular dynamics simulations of TEM-1 mutants. •Mutations effects on the mechanical properties are considered. •Mutants do not significantly alter the average enzymes structure. •Mutants produce sharp alterations in enzyme conformational repertoire. •Mutants also produce changes in the active site volume. -- Abstract: Molecular Dynamics simulations have been carried out in order to provide a molecular rationalization of the biological and thermodynamic differences observed for a class of TEM β-lactamases. In particular we have considered the TEM-1(wt), the single point mutants TEM-40 and TEM-19 representative of IRT and ESBL classes respectively, and TEM-1 mutant M182T, TEM-32 and TEM-20 which differ from the first three for the additional of M182T mutation. Results indicate that most of the thermodynamic, and probably biological behaviour of these systems arise from subtle effects which, starting from the alterations of the local interactions, produce drastic modifications of the conformational space spanned by the enzymes. The present study suggests that systems showing essentially the same secondary and tertiary structure may differentiate their chemical–biological activity essentially (and probably exclusively) on the basis of the thermal fluctuations occurring in their physiological environment.
- Authors:
-
- Dipartimento di Scienze Fisiche e Chimiche, Universita’ degli Studi di l’Aquila, Via Vetoio snc, 67100 Coppito (AQ) (Italy)
- Department of Health Sciences, Univ. of L’Aquila, 67010 L’Aquila (Italy)
- Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Università degli Studi di l’Aquila, Via Vetoio snc, 67100 Coppito (AQ) (Italy)
- Publication Date:
- OSTI Identifier:
- 22239665
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 436; Journal Issue: 4; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ENZYMES; GENE MUTATIONS; MECHANICAL PROPERTIES; MOLECULAR DYNAMICS METHOD; MUTANTS; SIMULATION
Citation Formats
Giampaolo, Alessia Di, Mazza, Fernando, Daidone, Isabella, Amicosante, Gianfranco, Perilli, Mariagrazia, and Aschi, Massimiliano. On the structural affinity of macromolecules with different biological properties: Molecular dynamics simulations of a series of TEM-1 mutants. United States: N. p., 2013.
Web. doi:10.1016/J.BBRC.2013.06.013.
Giampaolo, Alessia Di, Mazza, Fernando, Daidone, Isabella, Amicosante, Gianfranco, Perilli, Mariagrazia, & Aschi, Massimiliano. On the structural affinity of macromolecules with different biological properties: Molecular dynamics simulations of a series of TEM-1 mutants. United States. https://doi.org/10.1016/J.BBRC.2013.06.013
Giampaolo, Alessia Di, Mazza, Fernando, Daidone, Isabella, Amicosante, Gianfranco, Perilli, Mariagrazia, and Aschi, Massimiliano. 2013.
"On the structural affinity of macromolecules with different biological properties: Molecular dynamics simulations of a series of TEM-1 mutants". United States. https://doi.org/10.1016/J.BBRC.2013.06.013.
@article{osti_22239665,
title = {On the structural affinity of macromolecules with different biological properties: Molecular dynamics simulations of a series of TEM-1 mutants},
author = {Giampaolo, Alessia Di and Mazza, Fernando and Daidone, Isabella and Amicosante, Gianfranco and Perilli, Mariagrazia and Aschi, Massimiliano},
abstractNote = {Highlights: •We have performed molecular dynamics simulations of TEM-1 mutants. •Mutations effects on the mechanical properties are considered. •Mutants do not significantly alter the average enzymes structure. •Mutants produce sharp alterations in enzyme conformational repertoire. •Mutants also produce changes in the active site volume. -- Abstract: Molecular Dynamics simulations have been carried out in order to provide a molecular rationalization of the biological and thermodynamic differences observed for a class of TEM β-lactamases. In particular we have considered the TEM-1(wt), the single point mutants TEM-40 and TEM-19 representative of IRT and ESBL classes respectively, and TEM-1 mutant M182T, TEM-32 and TEM-20 which differ from the first three for the additional of M182T mutation. Results indicate that most of the thermodynamic, and probably biological behaviour of these systems arise from subtle effects which, starting from the alterations of the local interactions, produce drastic modifications of the conformational space spanned by the enzymes. The present study suggests that systems showing essentially the same secondary and tertiary structure may differentiate their chemical–biological activity essentially (and probably exclusively) on the basis of the thermal fluctuations occurring in their physiological environment.},
doi = {10.1016/J.BBRC.2013.06.013},
url = {https://www.osti.gov/biblio/22239665},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 436,
place = {United States},
year = {Fri Jul 12 00:00:00 EDT 2013},
month = {Fri Jul 12 00:00:00 EDT 2013}
}