The pathway for O2 diffusion inside CotA laccase and possible implications on the multicopper oxidases family

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8 Citations (Scopus)

Abstract

Laccases and multicopper oxidases (MCOs) oxidize a wide range of organic compounds while reducing O2 to water, enabling numerous biotechnological applications. It is still unknown how O2 reaches the internalized catalytic center of MCOs where it gets reduced, despite a proposed channel inferred from X-ray crystallography structures. Herein, an alternative new pathway is found through the use of a combination of free energy calculations (implicit ligand sampling), landscape analysis, and Markov modeling. The reported pathway is shown to be the one mostly contributing to O2 reaching the catalytic center. This pathway is considered in light of the whole MCO family, and a relation to the protonation state of a structurally conserved acidic residue right above the center is advanced.

Original languageEnglish
Pages (from-to)3525-3531
Number of pages7
JournalJournal Of Chemical Theory And Computation
Volume10
Issue number8
DOIs
Publication statusPublished - 12 Aug 2014

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Laccase
oxidase
Oxidoreductases
Protonation
X ray crystallography
organic compounds
Organic compounds
Free energy
crystallography
sampling
free energy
Ligands
Sampling
ligands
Water
water
x rays

Cite this

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title = "The pathway for O2 diffusion inside CotA laccase and possible implications on the multicopper oxidases family",
abstract = "Laccases and multicopper oxidases (MCOs) oxidize a wide range of organic compounds while reducing O2 to water, enabling numerous biotechnological applications. It is still unknown how O2 reaches the internalized catalytic center of MCOs where it gets reduced, despite a proposed channel inferred from X-ray crystallography structures. Herein, an alternative new pathway is found through the use of a combination of free energy calculations (implicit ligand sampling), landscape analysis, and Markov modeling. The reported pathway is shown to be the one mostly contributing to O2 reaching the catalytic center. This pathway is considered in light of the whole MCO family, and a relation to the protonation state of a structurally conserved acidic residue right above the center is advanced.",
author = "Damas, {Jo{\~a}o M.} and Baptista, {Ant{\'o}nio M.} and Soares, {Cl{\'a}udio M.}",
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T1 - The pathway for O2 diffusion inside CotA laccase and possible implications on the multicopper oxidases family

AU - Damas, João M.

AU - Baptista, António M.

AU - Soares, Cláudio M.

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AB - Laccases and multicopper oxidases (MCOs) oxidize a wide range of organic compounds while reducing O2 to water, enabling numerous biotechnological applications. It is still unknown how O2 reaches the internalized catalytic center of MCOs where it gets reduced, despite a proposed channel inferred from X-ray crystallography structures. Herein, an alternative new pathway is found through the use of a combination of free energy calculations (implicit ligand sampling), landscape analysis, and Markov modeling. The reported pathway is shown to be the one mostly contributing to O2 reaching the catalytic center. This pathway is considered in light of the whole MCO family, and a relation to the protonation state of a structurally conserved acidic residue right above the center is advanced.

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