De Novo Design of an Allosteric Metalloprotein Assembly with Strained Disulfide Bonds

Churchfield, L.A.; Medina-Morales, A.M.; Brodin, Jeffrey D.; Pérez, Alfredo; Tezcan, F.A.

doi:10.1021/jacs.6b08458

Cited by 40 publications

(62 citation statements)

References 31 publications

(70 reference statements)

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“…A hydrolytic mechanism of cleavage of a disulfide bond (Fig. 2C) was recently discovered in an engineered protein (59). A tetrameric metalloprotein with disulfide bonds at the subunit interfaces was constructed, and removal of the tetramer's four Zn 2ϩ ions resulted in cleavage of one of the bonds.…”

Section: Hydrolysismentioning

confidence: 99%

Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation

Chiu

Hogg

2019

Journal of Biological Chemistry

103

115

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Section: Hydrolysismentioning

confidence: 99%

Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation

Chiu

Hogg

2019

Journal of Biological Chemistry

103

115

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“…Directed evolution rounds are then used to improve the activities of the constructs. Interestingly, the obtained architectures are characterized by a structural flexibility that could be exploited to engineering allosteric control, as demonstrated in Ref .…”

Section: Enzyme Designmentioning

confidence: 87%

Protein design: from computer models to artificial intelligence

Paladino

Marchetti

Rinaldi

et al. 2017

WIREs Comput Mol Sci

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The rational design of novel biomolecules with desired functional properties is one of the most fascinating challenges in science, with implications at the fundamental and practical levels. From the fundamental point of view, the design of proteins able to support nonnatural reactivities represents the decisive test on our understanding of the molecular mechanisms through which biomolecules operate. From the practical point of view, new designs may open the way to applications in a wide variety of fields, ranging from health to life science, and from catalysis to material sciences. During the past decades, we have witnessed an amazing transition in the application of computational methods to protein and enzyme design, from simple fold prediction to ab initio structural design. Herein, we review key areas and fundamental aspects of research in the design of protein structures, interactions, and reactivities. We also provide our perspective on the exciting range of developments that are made possible by the integration of innovations in hardware, software, and theory, while keeping an eye on the applications, challenges, and opportunities that can open up in many different domains of science. WIREs Comput Mol Sci 2017, 7:e1318. doi: 10.1002/wcms.1318 This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods

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“…rational chemical design of 3D protein crystals) (Figs. 1g, 4g) (Sontz et al 2015;Bailey et al 2017), and an allosteric metalloprotein assembly with strained disulfide bonds (Churchfield et al 2016). Also, self-assembly of coherently dynamic, auxetic, two-dimensional protein crystals was reported (Suzuki et al 2016).…”

Section: Hierarchical Design Of Quaternary and Supra-quaternary Strucmentioning

confidence: 97%

Hierarchical design of artificial proteins and complexes toward synthetic structural biology

Arai

2017

Biophys Rev

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In multiscale structural biology, synthetic approaches are important to demonstrate biophysical principles and mechanisms underlying the structure, function, and action of bio-nanomachines. A central goal of "synthetic structural biology" is the design and construction of artificial proteins and protein complexes as desired. In this paper, I review recent remarkable progress of an array of approaches for hierarchical design of artificial proteins and complexes that signpost the path forward toward synthetic structural biology as an emerging interdisciplinary field. Topics covered include combinatorial and protein-engineering approaches for directed evolution of artificial binding proteins and membrane proteins, binary code strategy for structural and functional de novo proteins, protein nanobuilding block strategy for constructing nano-architectures, protein-metal-organic frameworks for 3D protein complex crystals, and rational and computational approaches for design/creation of artificial proteins and complexes, novel protein folds, ideal/optimized protein structures, novel binding proteins for targeted therapeutics, and self-assembling nanomaterials. Protein designers and engineers look toward a bright future in synthetic structural biology for the next generation of biophysics and biotechnology.

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De Novo Design of an Allosteric Metalloprotein Assembly with Strained Disulfide Bonds

Cited by 40 publications

References 31 publications

Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation

Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation

Protein design: from computer models to artificial intelligence

Hierarchical design of artificial proteins and complexes toward synthetic structural biology

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