Dynamics fingerprint and inherent asymmetric flexibility of a cold-adapted homodimeric enzyme. A case study of the Vibrio alkaline phosphatase

Elena Papaleo; Giulia Renzetti; Gaetano Invernizzi; Bjarni Ásgeirsson

doi:10.1016/j.bbagen.2012.12.011

Dynamics fingerprint and inherent asymmetric flexibility of a cold-adapted homodimeric enzyme. A case study of the Vibrio alkaline phosphatase

Elena Papaleo, Giulia Renzetti, Gaetano Invernizzi, Bjarni Ásgeirsson

Faculty of Physical Sciences

University of Iceland

Research output: Contribution to journal › Article › peer-review

Abstract

Background Protein dynamics influence protein function and stability and modulate conformational changes. Such motions depend on the underlying networks of intramolecular interactions and communicating residues within the protein structure. Here, we provide the first characterization of the dynamic fingerprint of the dimeric alkaline phosphatase (AP) from the cold-adapted Vibrio strain G15-21 (VAP), which is among the APs with the highest known k _cat at low temperatures. Methods Multiple all-atom explicit solvent molecular dynamics simulations were employed in conjunction with different metrics to analyze the dynamical patterns and the paths of intra- and intermolecular communication. Results Interactions and coupled motions at the interface between the two VAP subunits have been characterized, along with the networks of intramolecular interactions. It turns out a low number of intermolecular interactions and coupled motions, which result differently distributed in the two monomers. The paths of long-range communication mediated from the catalytic residues to distal sites were also characterized, pointing out a different information flow in the two subunits. Conclusions A pattern of asymmetric flexibility is evident in the two identical subunits of the VAP dimer that is intimately linked to a different distribution of intra- and intermolecular interactions. The asymmetry was also evident in pairs of cross-correlated residues during the dynamics. General significance The results here discussed provide a structural rationale to the half-of-site mechanism previously proposed for VAP and other APs, as well as a general framework to characterize asymmetric dynamics in homomeric enzymes.

Original language	English
Pages (from-to)	2970-2980
Number of pages	11
Journal	Biochimica et Biophysica Acta - General Subjects
Volume	1830
Issue number	4
DOIs	https://doi.org/10.1016/j.bbagen.2012.12.011
Publication status	Published - Apr 2013

Bibliographical note

Funding Information: The authors also would like also to thank Matteo Tiberti for all the fruitful comments and technical assistance in several steps of this work. B.A. extends gratitude to the Icelandic National Research Council (RANNIS) and the University of Iceland Research Fund for supporting the project financially. Funding Information: This research was supported by CASPUR (Consorzio Interuniversitario per le Applicazioni di Supercalcolo per Universita' e Ricerca) Standard HPC grant 2011 and 2012 to E.P. and G.I. The authors would like to thank Hannes Jonsson for providing access to the Sol computer cluster at the Science Institute of the University of Iceland, where part of the simulations was carried out.

Other keywords

Alkaline phosphatase
Asymmetric flexibility
Cold-adapted
Crown domain
Molecular dynamics
Psychrophilic

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10.1016/j.bbagen.2012.12.011

Cite this

@article{840bb7078cf94dbcac6eb2063c0ecc6e,

title = "Dynamics fingerprint and inherent asymmetric flexibility of a cold-adapted homodimeric enzyme. A case study of the Vibrio alkaline phosphatase",

abstract = "Background Protein dynamics influence protein function and stability and modulate conformational changes. Such motions depend on the underlying networks of intramolecular interactions and communicating residues within the protein structure. Here, we provide the first characterization of the dynamic fingerprint of the dimeric alkaline phosphatase (AP) from the cold-adapted Vibrio strain G15-21 (VAP), which is among the APs with the highest known k cat at low temperatures. Methods Multiple all-atom explicit solvent molecular dynamics simulations were employed in conjunction with different metrics to analyze the dynamical patterns and the paths of intra- and intermolecular communication. Results Interactions and coupled motions at the interface between the two VAP subunits have been characterized, along with the networks of intramolecular interactions. It turns out a low number of intermolecular interactions and coupled motions, which result differently distributed in the two monomers. The paths of long-range communication mediated from the catalytic residues to distal sites were also characterized, pointing out a different information flow in the two subunits. Conclusions A pattern of asymmetric flexibility is evident in the two identical subunits of the VAP dimer that is intimately linked to a different distribution of intra- and intermolecular interactions. The asymmetry was also evident in pairs of cross-correlated residues during the dynamics. General significance The results here discussed provide a structural rationale to the half-of-site mechanism previously proposed for VAP and other APs, as well as a general framework to characterize asymmetric dynamics in homomeric enzymes.",

keywords = "Alkaline phosphatase, Asymmetric flexibility, Cold-adapted, Crown domain, Molecular dynamics, Psychrophilic",

author = "Elena Papaleo and Giulia Renzetti and Gaetano Invernizzi and Bjarni {\'A}sgeirsson",

note = "Funding Information: The authors also would like also to thank Matteo Tiberti for all the fruitful comments and technical assistance in several steps of this work. B.A. extends gratitude to the Icelandic National Research Council (RANNIS) and the University of Iceland Research Fund for supporting the project financially. Funding Information: This research was supported by CASPUR (Consorzio Interuniversitario per le Applicazioni di Supercalcolo per Universita' e Ricerca) Standard HPC grant 2011 and 2012 to E.P. and G.I. The authors would like to thank Hannes Jonsson for providing access to the Sol computer cluster at the Science Institute of the University of Iceland, where part of the simulations was carried out.",

year = "2013",

month = apr,

doi = "10.1016/j.bbagen.2012.12.011",

language = "English",

volume = "1830",

pages = "2970--2980",

journal = "Biochimica et Biophysica Acta - General Subjects",

issn = "0304-4165",

publisher = "Elsevier",

number = "4",

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T1 - Dynamics fingerprint and inherent asymmetric flexibility of a cold-adapted homodimeric enzyme. A case study of the Vibrio alkaline phosphatase

AU - Papaleo, Elena

AU - Renzetti, Giulia

AU - Invernizzi, Gaetano

AU - Ásgeirsson, Bjarni

N1 - Funding Information: The authors also would like also to thank Matteo Tiberti for all the fruitful comments and technical assistance in several steps of this work. B.A. extends gratitude to the Icelandic National Research Council (RANNIS) and the University of Iceland Research Fund for supporting the project financially. Funding Information: This research was supported by CASPUR (Consorzio Interuniversitario per le Applicazioni di Supercalcolo per Universita' e Ricerca) Standard HPC grant 2011 and 2012 to E.P. and G.I. The authors would like to thank Hannes Jonsson for providing access to the Sol computer cluster at the Science Institute of the University of Iceland, where part of the simulations was carried out.

PY - 2013/4

Y1 - 2013/4

N2 - Background Protein dynamics influence protein function and stability and modulate conformational changes. Such motions depend on the underlying networks of intramolecular interactions and communicating residues within the protein structure. Here, we provide the first characterization of the dynamic fingerprint of the dimeric alkaline phosphatase (AP) from the cold-adapted Vibrio strain G15-21 (VAP), which is among the APs with the highest known k cat at low temperatures. Methods Multiple all-atom explicit solvent molecular dynamics simulations were employed in conjunction with different metrics to analyze the dynamical patterns and the paths of intra- and intermolecular communication. Results Interactions and coupled motions at the interface between the two VAP subunits have been characterized, along with the networks of intramolecular interactions. It turns out a low number of intermolecular interactions and coupled motions, which result differently distributed in the two monomers. The paths of long-range communication mediated from the catalytic residues to distal sites were also characterized, pointing out a different information flow in the two subunits. Conclusions A pattern of asymmetric flexibility is evident in the two identical subunits of the VAP dimer that is intimately linked to a different distribution of intra- and intermolecular interactions. The asymmetry was also evident in pairs of cross-correlated residues during the dynamics. General significance The results here discussed provide a structural rationale to the half-of-site mechanism previously proposed for VAP and other APs, as well as a general framework to characterize asymmetric dynamics in homomeric enzymes.

AB - Background Protein dynamics influence protein function and stability and modulate conformational changes. Such motions depend on the underlying networks of intramolecular interactions and communicating residues within the protein structure. Here, we provide the first characterization of the dynamic fingerprint of the dimeric alkaline phosphatase (AP) from the cold-adapted Vibrio strain G15-21 (VAP), which is among the APs with the highest known k cat at low temperatures. Methods Multiple all-atom explicit solvent molecular dynamics simulations were employed in conjunction with different metrics to analyze the dynamical patterns and the paths of intra- and intermolecular communication. Results Interactions and coupled motions at the interface between the two VAP subunits have been characterized, along with the networks of intramolecular interactions. It turns out a low number of intermolecular interactions and coupled motions, which result differently distributed in the two monomers. The paths of long-range communication mediated from the catalytic residues to distal sites were also characterized, pointing out a different information flow in the two subunits. Conclusions A pattern of asymmetric flexibility is evident in the two identical subunits of the VAP dimer that is intimately linked to a different distribution of intra- and intermolecular interactions. The asymmetry was also evident in pairs of cross-correlated residues during the dynamics. General significance The results here discussed provide a structural rationale to the half-of-site mechanism previously proposed for VAP and other APs, as well as a general framework to characterize asymmetric dynamics in homomeric enzymes.

KW - Alkaline phosphatase

KW - Asymmetric flexibility

KW - Cold-adapted

KW - Crown domain

KW - Molecular dynamics

KW - Psychrophilic

UR - https://www.scopus.com/pages/publications/84873734964

U2 - 10.1016/j.bbagen.2012.12.011

DO - 10.1016/j.bbagen.2012.12.011

M3 - Article

C2 - 23266619

SN - 0304-4165

VL - 1830

SP - 2970

EP - 2980

JO - Biochimica et Biophysica Acta - General Subjects

JF - Biochimica et Biophysica Acta - General Subjects

IS - 4

ER -

Dynamics fingerprint and inherent asymmetric flexibility of a cold-adapted homodimeric enzyme. A case study of the Vibrio alkaline phosphatase

Abstract

Bibliographical note

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