Simulating Substrate Recognition and Oxidation in Laccases: From Description to Design

Maria Fátima Lucas; Emanuele Monza; Lise Juel Jørgensen; Heidi Asschenfeldt Ernst; Klaus Piontek; Morten Jannik Bjerrum; Ángel T. Martinez; Susana Camarero; Víctor Guallar

doi:10.1021/acs.jctc.6b01158

Simulating Substrate Recognition and Oxidation in Laccases: From Description to Design

Maria Fátima Lucas^*, Emanuele Monza, Lise Juel Jørgensen, Heidi Asschenfeldt Ernst, Klaus Piontek, Morten Jannik Bjerrum, Ángel T. Martinez, Susana Camarero, Víctor Guallar

^*Corresponding author for this work

Department of Chemistry

15 Citations (Scopus)

41 Downloads (Pure)

Abstract

To meet the very specific requirements demanded by industry, proteins must be appropriately tailored. Engineering laccases, to improve the oxidation of small molecules, with applications in multiple fields, is, however, a difficult task. Most efforts have concentrated on increasing the redox potential of the enzyme, but in recent work, we have pursued an alternate strategy to engineering these biocatalysts. In particular, we have found that redesigning substrate binding at the T1 pocket, guided by in silico methodologies, to be a more consistent option. In this work, we evaluate the robustness of our computational approach to estimate activity, emphasizing the importance of the binding event in laccase reactivity. Strengths and weaknesses of the protocol are discussed along with its potential for scoring large numbers of protein sequences and thus its significance in protein engineering.

Original language	English
Journal	Journal of Chemical Theory and Computation
Volume	13
Issue number	3
Pages (from-to)	1462-1467
Number of pages	6
ISSN	1549-9618
DOIs	https://doi.org/10.1021/acs.jctc.6b01158
Publication status	Published - 2017

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title = "Simulating Substrate Recognition and Oxidation in Laccases: From Description to Design",

abstract = "To meet the very specific requirements demanded by industry, proteins must be appropriately tailored. Engineering laccases, to improve the oxidation of small molecules, with applications in multiple fields, is, however, a difficult task. Most efforts have concentrated on increasing the redox potential of the enzyme, but in recent work, we have pursued an alternate strategy to engineering these biocatalysts. In particular, we have found that redesigning substrate binding at the T1 pocket, guided by in silico methodologies, to be a more consistent option. In this work, we evaluate the robustness of our computational approach to estimate activity, emphasizing the importance of the binding event in laccase reactivity. Strengths and weaknesses of the protocol are discussed along with its potential for scoring large numbers of protein sequences and thus its significance in protein engineering.",

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doi = "10.1021/acs.jctc.6b01158",

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T1 - Simulating Substrate Recognition and Oxidation in Laccases

T2 - From Description to Design

AU - Lucas, Maria Fátima

AU - Monza, Emanuele

AU - Jørgensen, Lise Juel

AU - Ernst, Heidi Asschenfeldt

AU - Piontek, Klaus

AU - Bjerrum, Morten Jannik

AU - Martinez, Ángel T.

AU - Camarero, Susana

AU - Guallar, Víctor

PY - 2017

Y1 - 2017

N2 - To meet the very specific requirements demanded by industry, proteins must be appropriately tailored. Engineering laccases, to improve the oxidation of small molecules, with applications in multiple fields, is, however, a difficult task. Most efforts have concentrated on increasing the redox potential of the enzyme, but in recent work, we have pursued an alternate strategy to engineering these biocatalysts. In particular, we have found that redesigning substrate binding at the T1 pocket, guided by in silico methodologies, to be a more consistent option. In this work, we evaluate the robustness of our computational approach to estimate activity, emphasizing the importance of the binding event in laccase reactivity. Strengths and weaknesses of the protocol are discussed along with its potential for scoring large numbers of protein sequences and thus its significance in protein engineering.

AB - To meet the very specific requirements demanded by industry, proteins must be appropriately tailored. Engineering laccases, to improve the oxidation of small molecules, with applications in multiple fields, is, however, a difficult task. Most efforts have concentrated on increasing the redox potential of the enzyme, but in recent work, we have pursued an alternate strategy to engineering these biocatalysts. In particular, we have found that redesigning substrate binding at the T1 pocket, guided by in silico methodologies, to be a more consistent option. In this work, we evaluate the robustness of our computational approach to estimate activity, emphasizing the importance of the binding event in laccase reactivity. Strengths and weaknesses of the protocol are discussed along with its potential for scoring large numbers of protein sequences and thus its significance in protein engineering.

U2 - 10.1021/acs.jctc.6b01158

DO - 10.1021/acs.jctc.6b01158

M3 - Journal article

C2 - 28187256

AN - SCOPUS:85015289419

SN - 1549-9618

VL - 13

SP - 1462

EP - 1467

JO - Journal of Chemical Theory and Computation

JF - Journal of Chemical Theory and Computation

IS - 3

ER -

Simulating Substrate Recognition and Oxidation in Laccases: From Description to Design

Abstract

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