Copper-Containing Catalytic Amyloids Promote Phosphoester Hydrolysis and Tandem Reactions

Lengyel‐Zhand, Zsofia; Rufo, Caroline M.; Moroz, Yurii S.; Makhlynets, Olga V.; Korendovych, Ivan V.

doi:10.1021/acscatal.7b03323

Cited by 89 publications

(94 citation statements)

References 34 publications

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“…While other methods such as SELEX have been used successfully to screen for RNA-based structures that recognize small molecules, [38][39][40] peptides provide greater functional versatility due to the availability of twenty different building blocks. In future these simple building blocks, combined with insights from peptide-based catalyst design [41,42] could guide the development of components of active bioinspired materials that are fueled by nucleotides. [10,11,43] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57…”

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confidence: 99%

Unbiased Discovery of Dynamic Peptide‐ATP Complexes

et al. 2019

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Minimalistic peptides are attractive as components for the design of active bio-inspired materials that perform their functions enabled by the continuous turnover of chemical fuels. The first requirement for such systems is chemical complexation with the fuel source. Herein, we demonstrate the unbiased screening for heptapeptides that recognize adenosine triphosphate (ATP), life's ubiquitous energy source, using the in vitro method phage display. Characterization of the identified lead sequence by NMR spectroscopy and molecular dynamics simulations revealed peptide-ATP complexes that are highly dynamic and take on an ensemble of conformations. Systematic investigation of Ala variants of the identified peptide revealed the contribution of individual residues to association with the nucleotide. Importantly, the identified heptapeptide sequence is not related to any known nucleotide-binding motif. Our results demonstrate the application of phage display for de novo selection of short peptides that adapt their conformational space through recognition of a small molecule and provides a first step toward the design of peptide-based ATP-metabolizing structures.The complex functionality of biological systems arises from the integration of numerous molecular processes that lead to functions which exceed the sum of the characteristics of their constituents, referred to as emergent properties. [1] These processes include molecular recognition, supramolecular self-assembly and chemical reactivity, enabling systems to rapidly adapt and change their functions while turning over chemical fuels, thereby enabling dynamic processes which operate far from the thermodynamic equilibrium. [2,3] In order to identify molecular components which display these key functions, both computational and experimental methods have been developed that enable searching a large molecular space for interactions between molecules in order to predict potential emergent properties within a system. [4,5] Despite enormous progress in supramolecular systems design, [3,6,7] and its importance to materials science, biotechnology and biomedical engineering, the design of active and adaptive systems with designed functions remains a challenge. [8] Adenosine triphosphate (ATP) is the ubiquitous energy currency that maintains the dynamic structures and functions of living cells. [9] Hydrolysis of the nucleotide releases 28 kJ/mol free energy and thus makes it an attractive candidate to fuel minimalistic active structures that may be integrated within living systems in the future. Our ultimate goal is to develop ATP metabolizing matter based on designed peptides. In here, we describe a first important step, the identification of novel peptides that recruit ATP and form dynamic complexes with it.Reported examples of chemically fueled assembly that utilize nucleotides as energy source rely on biological enzymes. [10][11][12] Efforts to identify minimalistic peptide sequences that interact with nucleotides are based on rational mimicry and simplification of working p...

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confidence: 99%

Unbiased Discovery of Dynamic Peptide‐ATP Complexes

et al. 2019

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“…Catalytic amyloids show catalytic efficiencies that rival those of natural enzymes by weight and can facilitate hydrolytic and redox transformations as well as tandem reactions . However, none of the successful examples of catalytic amyloids reported have been able to take advantage of the incredible potential of complex metal‐containing cofactors.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we have developed a series of seven‐residue peptides capable of self‐assembly in the presence of transition‐metal ions to form catalytic amyloids that promote hydrolytic and redox transformations . Firstly, we have tested the ability of these peptides to coordinate hemin.…”

Section: Methodsmentioning

confidence: 99%

Semi‐Rationally Designed Short Peptides Self‐Assemble and Bind Hemin to Promote Cyclopropanation

Zozulia

Korendovych

2020

Angew Chem Int Ed

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The self‐assembly of short peptides gives rise to versatile nanoassemblies capable of promoting efficient catalysis. We have semi‐rationally designed a series of seven‐residue peptides that form hemin‐binding catalytic amyloids to facilitate enantioselective cyclopropanation with efficiencies that rival those of engineered hemin proteins. These results demonstrate that: 1) Catalytic amyloids can bind complex metallocofactors to promote practically important multisubstrate transformations. 2) Even essentially flat surfaces of amyloid assemblies can impart a substantial degree of enantioselectivity without the need for extensive optimization. 3) The ease of peptide preparation allows for straightforward incorporation of unnatural amino acids and the preparation of peptides made from d‐amino acids with complete reversal of enantioselectivity.

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“…Korendovych and coworkers found that metal-binding amyloidogenic short peptides displayed hydrolytic activity [ 60 , 61 ]. Recently, they installed a binding site for Fe-protoporphyrin IX 31 on a β-sheet amyloid for the cyclopropanation reaction ( Figure 7 , reaction iv) [ 62 ].…”

Section: Recent Progress On the Various Reactions Catalyzed By Armmentioning

confidence: 99%

Artificial Metalloenzymes: From Selective Chemical Transformations to Biochemical Applications

Himiyama

Okamoto

2020

Molecules

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Artificial metalloenzymes (ArMs) comprise a synthetic metal complex in a protein scaffold. ArMs display performances combining those of both homogeneous catalysts and biocatalysts. Specifically, ArMs selectively catalyze non-natural reactions and reactions inspired by nature in water under mild conditions. In the past few years, the construction of ArMs that possess a genetically incorporated unnatural amino acid and the directed evolution of ArMs have become of great interest in the field. Additionally, biochemical applications of ArMs have steadily increased, owing to the fact that compartmentalization within a protein scaffold allows the synthetic metal complex to remain functional in a sea of inactivating biomolecules. In this review, we present updates on: (1) the newly reported ArMs, according to their type of reaction, and (2) the unique biochemical applications of ArMs, including chemoenzymatic cascades and intracellular/in vivo catalysis. We believe that ArMs have great potential as catalysts for organic synthesis and as chemical biology tools for pharmaceutical applications.

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Copper-Containing Catalytic Amyloids Promote Phosphoester Hydrolysis and Tandem Reactions

Cited by 89 publications

References 34 publications

Unbiased Discovery of Dynamic Peptide‐ATP Complexes

Unbiased Discovery of Dynamic Peptide‐ATP Complexes

Semi‐Rationally Designed Short Peptides Self‐Assemble and Bind Hemin to Promote Cyclopropanation

Artificial Metalloenzymes: From Selective Chemical Transformations to Biochemical Applications

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