A De Novo-Designed Type 3 Copper Protein Tunes Catechol Substrate Recognition and Reactivity.

Artificial Metalloenzymes Phenol Oxidases Protein Design Substrate Selectivity T3 di-Copper Site

Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
02 01 2023
Historique:
received: 05 08 2022
pubmed: 6 11 2022
medline: 31 12 2022
entrez: 5 11 2022
Statut: ppublish

Résumé

De novo metalloprotein design is a remarkable approach to shape protein scaffolds toward specific functions. Here, we report the design and characterization of Due Rame 1 (DR1), a de novo designed protein housing a di-copper site and mimicking the Type 3 (T3) copper-containing polyphenol oxidases (PPOs). To achieve this goal, we hierarchically designed the first and the second di-metal coordination spheres to engineer the di-copper site into a simple four-helix bundle scaffold. Spectroscopic, thermodynamic, and functional characterization revealed that DR1 recapitulates the T3 copper site, supporting different copper redox states, and being active in the O

Identifiants

pubmed: 36334012
doi: 10.1002/anie.202211552
doi:

Substances chimiques

Copper 789U1901C5
catechol LF3AJ089DQ
Catechols 0
Metalloproteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202211552

Informations de copyright

© 2022 Wiley-VCH GmbH.

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Auteurs

Fabio Pirro (F)

Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Naples, Italy.

Salvatore La Gatta (S)

Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Naples, Italy.

Federica Arrigoni (F)

Department of Biotechnology and Biosciences, University of Milan-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy.

Antonino Famulari (A)

Department of Chemistry, University of Torino, Via Giuria 9, 10125, Torino, Italy.
Department of Condensed Matter Physics, University of of Zaragoza, Calle Pedro Cerbuna 12, 50009, Zaragoza, Spain.

Ornella Maglio (O)

Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Naples, Italy.
Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Pietro Castellino 111, 80131, Napoli, Italy.

Pompea Del Vecchio (P)

Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Naples, Italy.

Mario Chiesa (M)

Department of Chemistry, University of Torino, Via Giuria 9, 10125, Torino, Italy.

Luca De Gioia (L)

Department of Biotechnology and Biosciences, University of Milan-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy.

Luca Bertini (L)

Department of Biotechnology and Biosciences, University of Milan-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy.

Marco Chino (M)

Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Naples, Italy.

Flavia Nastri (F)

Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Naples, Italy.

Angela Lombardi (A)

Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Naples, Italy.

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