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 af dette arbejde

Kemisk Institut

15 Citationer (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

Originalsprog	Engelsk
Tidsskrift	Journal of Chemical Theory and Computation
Vol/bind	13
Udgave nummer	3
Sider (fra-til)	1462-1467
Antal sider	6
ISSN	1549-9618
DOI	https://doi.org/10.1021/acs.jctc.6b01158
Status	Udgivet - 2017

Adgang til dokumentet

10.1021/acs.jctc.6b01158

Lucas-JCTC-accepted-2017Indsendt manuskript, 918 KB

Citationsformater

@article{3f066f693bfc460ca9b7f228b0b7a961,

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.",

author = "Lucas, {Maria F{\'a}tima} and Emanuele Monza and J{\o}rgensen, {Lise Juel} and Ernst, {Heidi Asschenfeldt} and Klaus Piontek and Bjerrum, {Morten Jannik} and Martinez, {{\'A}ngel T.} and Susana Camarero and V{\'i}ctor Guallar",

year = "2017",

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

language = "English",

volume = "13",

pages = "1462--1467",

journal = "Journal of Chemical Theory and Computation",

issn = "1549-9618",

publisher = "American Chemical Society",

number = "3",

}

TY - JOUR

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

Adgang til dokumentet

Fingeraftryk

Citationsformater