Engineering Metalloprotein Functions in Designed and Native Scaffolds

Nastri, Flavia; D’Alonzo, Daniele; Leone, Linda; Zambrano, Gerardo; Pavone, Vincenzo; Lombardi, Angela

doi:10.1016/j.tibs.2019.06.006

Cited by 89 publications

(76 citation statements)

References 142 publications

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“…There are numerous approaches for the de novo design of a metalloprotein and an even larger number of designed scaffolds to work with . There have been many reviews on the subject of metalloprotein design for catalysis, including an entire issue of Accounts of Chemical Research . Therefore, this Review highlights recent developments using purely alpha‐helical structures, specifically using three‐stranded coiled‐coil peptides (3SCCs) and three helix bundle (3HB) proteins, emphasizing research from our group.…”

Section: Introductionmentioning

confidence: 99%

Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds

2020

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Section: Introductionmentioning

confidence: 99%

Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds

2020

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“…The field of metalloenzyme design and engineering is approaching its "golden age." By using several tools and complementary strategies, protein designers are capable of implanting a variety of functions into native or designed protein scaffolds [1,18]. The research field now appears to have limitless potential, as protein scaffolds can be shaped, optimized, or repurposed to obtain artificial catalysts highly competent toward specific functions.…”

Section: Introductionmentioning

confidence: 99%

“…The research field now appears to have limitless potential, as protein scaffolds can be shaped, optimized, or repurposed to obtain artificial catalysts highly competent toward specific functions. Indeed, several outstanding examples demonstrate that it is possible to obtain artificial metalloenzymes behaving as oxydases, oxygenases, and peroxidases [1,2,[8][9][10][11][12][13][14], hydrolases [1,2,[15][16][17], and hydrogenases [1,18,19,]. The astonishing Biotechnology and Applied Biochemistry potential of this field has further been disclosed by the development of artificial metalloenzymes able to catalyze reactions with unknown natural counterparts [5,[20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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Clickable artificial heme‐peroxidases for the development of functional nanomaterials

Zambrano

Chino

Renzi

et al. 2020

Biotech and App Biochem

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Artificial metalloenzymes as catalysts are promising candidates for their use in different technologies, such as bioremediation, biomass transformation, or biosensing. Despite this, their practical exploitation is still at an early stage. Immobilized natural enzymes have been proposed to enhance their applicability. Immobilization may offer several advantages: (i) catalyst reuse; (ii) easy separation of the enzyme from the reaction medium; (iii) better tolerance to harsh temperature and pH conditions. Here, we report an easy immobilization procedure of an artificial peroxidase on different surfaces, by means of click chemistry. FeMC6*a, a recently developed peroxidase mimic, has been functionalized with a pegylated aza‐dibenzocyclooctyne to afford a “clickable” biocatalyst, namely FeMC6*a‐PEG4@DBCO, which easily reacts with azide‐functionalized molecules and/or nanomaterials to afford functional bioconjugates. The clicked biocatalyst retains its structural and, to some extent, its functional behaviors, thus housing high potential for biotechnological applications.

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“…Protein design is able to not only reveal the structure-function relationship of native proteins, but also create artificial proteins with advanced functions [1][2][3][4][5][6][7][8][9][10][11][12]. This is especially the case for heme protein design, which has received much attention in the last few decades, and various approaches have been established for rational design, such as the introduction of non-heme metal ions and unnatural amino acids, and the use of heme mimics to act as an active site [1][2][3][4][5][6][7][8][9][10][11][12]. Importantly, computer modeling and molecular dynamics (MD) simulation play key roles in guiding the protein design [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulation and Kinetic Study of Fluoride Binding to V21C/V66C Myoglobin with a Cytoglobin-like Disulfide Bond

Yin

Wang

et al. 2020

IJMS

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Protein design is able to create artificial proteins with advanced functions, and computer simulation plays a key role in guiding the rational design. In the absence of structural evidence for cytoglobin (Cgb) with an intramolecular disulfide bond, we recently designed a de novo disulfide bond in myoglobin (Mb) based on structural alignment (i.e., V21C/V66C Mb double mutant). To provide deep insight into the regulation role of the Cys21-Cys66 disulfide bond, we herein perform molecular dynamics (MD) simulation of the fluoride–protein complex by using a fluoride ion as a probe, which reveals detailed interactions of the fluoride ion in the heme distal pocket, involving both the distal His64 and water molecules. Moreover, we determined the kinetic parameters of fluoride binding to the double mutant. The results agree with the MD simulation and show that the formation of the Cys21-Cys66 disulfide bond facilitates both fluoride binding to and dissociating from the heme iron. Therefore, the combination of theoretical and experimental studies provides valuable information for understanding the structure and function of heme proteins, as regulated by a disulfide bond. This study is thus able to guide the rational design of artificial proteins with tunable functions in the future.

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Engineering Metalloprotein Functions in Designed and Native Scaffolds

Cited by 89 publications

References 142 publications

Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds

Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds

Clickable artificial heme‐peroxidases for the development of functional nanomaterials

Molecular Dynamics Simulation and Kinetic Study of Fluoride Binding to V21C/V66C Myoglobin with a Cytoglobin-like Disulfide Bond

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