Work

A nanoengineered tandem nitroreductase: designing a robust prodrug-activating nanoreactor

Year: 2024

Type: article

Abstract: Nitroreductases are important enzymes for a variety of applications, including cancer therapy and bioremediation. They often require encapsulation to improve stability and activity. We focus on genetically encoded encapsulation of nitroreductases within protein capsids, like encapsulins. Our study showcases the encapsulation of nitroreductase NfsB as functional dimers within encapsulins, which enhances protein activity and stability in diverse conditions. Mutations within the pore region are beneficial for activity of the encapsulated enzyme, potentially by increasing diffusion rates. Cryogenic electron microscopy reveals the overall architecture of the encapsulated dimeric NfsB within the nanoreactor environment and identifies multiple pore states in the shell. These findings highlight the potential of encapsulins as versatile tools for enhancing enzyme performance across various fields.

Source: RSC Chemical Biology

DOI: 10.1039/d4cb00127c

Authors: Mariia Zmyslia, Michael J. Capper, Michael Grimmeisen, Kerstin Sartory, Benedikt Deuringer, Mohamed Abdelsalam, Kaiwei Shen, Manfred Jung, Wolfgang Sippl, Hans-Georg Koch, Laurine Kaul, Regine Süss, Jesko Köhnke, Claudia Jessen-Trefzer

Institutions: University of Freiburg, University of Glasgow, Martin Luther University Halle-Wittenberg, Alexandria University, Leibniz University Hannover

Language: English

Topic: Enzyme Catalysis and Immobilization

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $1,962

Funders: Ministry of Higher Education and Scientific Research, Scottish Funding Council, Deutscher Akademischer Austauschdienst, Deutsche Forschungsgemeinschaft, Albert-Ludwigs-Universität Freiburg, China Scholarship Council, Medical Research Council, European Research Council

Awards: G1361465335, Epigenetische Kontrolle von Makrophagen in der LeishmanienInfektion, G1514386576, G1787402452, G1888663043, Structural biology and imaging platform, G259924242, G2685078022, G280210646, G2913978822, G2916166774, G3236052858, G3523822304, G3948179449, G4578989300, G4591285899, G4762306864, Entwicklung und biologische Charakterisierung von dualen Inhibitoren gegen den Apicomplexa Parasiten Plasmodium falciparum, EXC 2189: CIBSS Centre for Integrative Biological Signalling Studies, SFB 992: Medizinische Epigenetik (MEDEP) Von grundlegenden Mechanismen zu klinischen Anwendungen, G5292276475, Molekulares Design, Synthese und Pharmakologie von neuen und selektiven Histondesacetylase 10 (HDAC10) Inhibitoren, The Scottish Macromolecular Imaging Centre (SMIC), Accelerating throughput at Scotland's national Cryo-EM centre - a next generation direct electron detector for SCMI., G701413587, G7833425038, G7889660257, G8097560904, G8416743702, SFB 1381: Dynamische Organisation zellulärer Proteinmaschinerien: Von der Biogenese und modularen Assemblierung zur Funktion, G9000211058, G983559663

OpenAlex ID: W4404019688

FWCI: 1.278

Cites: 61

Cited by: 11

Related to: 10