Early evolution benefited from a complex network of reactions involving multiple C−C bond forming and breaking events that were critical for primitive metabolism. Nature gradually chose highly ...evolved and complex enzymes such as lyases to efficiently facilitate C−C bond formation and cleavage with remarkable substrate selectivity. Reported here is a lipidated short peptide which accesses a homogenous nanotubular morphology to efficiently catalyze C−C bond cleavage and formation. This system shows morphology‐dependent catalytic rates, suggesting the formation of a binding pocket and registered enhancements in the presence of the hydrogen‐bond donor tyrosine, which is exploited by extant aldolases. These assemblies showed excellent substrate selectivity and templated the formation of a specific adduct from a pool of possible adducts. The ability to catalyze metabolically relevant cascade transformations suggests the importance of such systems in early evolution.
Designer aldolases: Amyloid‐like lipidated peptide nanotubes demonstrate aldolase cascade activity with selectivity. Nanotubes having lysines as exposed residues bind to tyrosine to create an efficient catalyst which mimics aldolase activity. This system shows morphology‐dependent catalytic rates and suggests the importance of such systems in early evolution.
The Ebola virus (EBOV) envelope glycoprotein (GP) is a membrane fusion machine required for virus entry into cells. Following endocytosis of EBOV, the GP1 domain is cleaved by cellular cathepsins in ...acidic endosomes, removing the glycan cap and exposing a binding site for the Niemann-Pick C1 (NPC1) receptor. NPC1 binding to cleaved GP1 is required for entry. How this interaction translates to GP2 domain-mediated fusion of viral and endosomal membranes is not known. Here, using a bulk fluorescence dequenching assay and single-molecule Förster resonance energy transfer (smFRET)-imaging, we found that acidic pH, Ca2+, and NPC1 binding synergistically induce conformational changes in GP2 and permit virus-liposome lipid mixing. Acidic pH and Ca2+ shifted the GP2 conformational equilibrium in favor of an intermediate state primed for NPC1 binding. Glycan cap cleavage on GP1 enabled GP2 to transition from a reversible intermediate to an irreversible conformation, suggestive of the postfusion 6-helix bundle; NPC1 binding further promoted transition to the irreversible conformation. Thus, the glycan cap of GP1 may allosterically protect against inactivation of EBOV by premature triggering of GP2.
In extant biology, large and complex enzymes employ low molecular weight cofactors such as dihydronicotinamides as efficient hydride transfer agents and electron carriers for the regulation of ...critical metabolic processes. In absence of complex contemporary enzymes, these molecular cofactors are generally inefficient to facilitate any reactions on their own. Herein, we report short peptide-based amyloid nanotubes featuring exposed arrays of cationic and hydrophobic residues that can bind small molecular weak hydride transfer agents (NaBH
) to facilitate efficient reduction of ester substrates in water. In addition, the paracrystalline amyloid phases loaded with borohydrides demonstrate recyclability, substrate selectivity and controlled reduction and surpass the capabilities of standard reducing agent such as LiAlH
. The amyloid microphases and their collaboration with small molecular cofactors foreshadow the important roles that short peptide-based assemblies might have played in the emergence of protometabolism and biopolymer evolution in prebiotic earth.
Herein, we report the substrate induced generation of a transient catalytic microenvironment from a single amino acid functionalized fatty acid in presence of a cofactor hemin. The catalytic state ...accessed under non‐equilibrium conditions showed acceleration of peroxidase activity resulting in degradation of the substrate and subsequently led to disassembly. Equilibrated systems could not access the three‐dimensional microphases and showed substantially lower catalytic activity. Further, the assembled state showed latent catalytic function (promiscuity) to hydrolyze a precursor to yield the same substrate. Consequently, the assembly demonstrated protometabolism by exploiting the peroxidase‐hydrolase cascade to augment the lifetime and the mechanical properties of the catalytic state.
Substrate‐induced generation of a transient catalytic microphase was shown in presence of a single amino acid functionalized fatty acid and a cofactor hemin. The transient state exhibited acceleration of catalytic potential resulting in degradation of the substrate. Furthermore, latent catalytic function was displayed to hydrolyze a precursor to yield the same substrate suggesting promiscuous activity.
The protein-only infectious agents known as prions exist within cellular matrices as populations of assembled polypeptide phases ranging from particles to amyloid fibres. These phases appear to ...undergo Darwinian-like selection and propagation, yet remarkably little is known about their accessible chemical and biological functions. Here we construct simple peptides that assemble into well-defined amyloid phases and define paracrystalline surfaces able to catalyse specific enantioselective chemical reactions. Structural adjustments of individual amino acid residues predictably control both the assembled crystalline order and their accessible catalytic repertoire. Notably, the density and proximity of the extended arrays of enantioselective catalytic sites achieve template-directed polymerization of new polymers. These diverse amyloid templates can now be extended as dynamic self-propagating templates for the construction of even more complex functional materials.
The large scale fluctuations of the ordered state in active matter systems are usually characterized by studying the "giant number fluctuations" of particles in any finite volume, as compared to the ...expectations from the central limit theorem. However, in ordering systems, the fluctuations in density ordering are often captured through their structure functions deviating from Porod's law. In this Letter we study the relationship between giant number fluctuations and structure functions for different models of active matter as well as other nonequilibrium systems. A unified picture emerges, with different models falling in four distinct classes depending on the nature of their structure functions. For one class, we show that experimentalists may find Porod's law violation, by measuring subleading corrections to the number fluctuations.
The present work reports a new class of antibacterial hydrogelators based on anti-inflammatory N-fluorenyl-9-methoxycarbonyl (Fmoc) amino acid/peptides functionalized cationic amphiphiles. These ...positively charged hydrogelators were rationally designed and developed by the incorporation of a pyridinium moiety at the C-terminal of Fmoc amino acid/peptides, because the pyridinium-based amphiphiles are a known antibacterial agent due to their cell membrane penetration properties. The Fmoc amino acid/peptide-based cationic amphiphiles efficiently gelate (minimum gelation concentration ∼0.6−2.2%, w/v) water at room temperature. Judicious variation of amino acid and their sequences revealed the architectural dependence of the molecules on their gelation ability. Several microscopic techniques like field-emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) were used to obtain the visual insight of the morphology of the gel network. A number of spectroscopic techniques like circular dichroism, FTIR, photoluminescence, and XRD were utilized to know the involvement of several noncovalent interactions and participation of the different segments of the molecules during gelation. Spectroscopic results showed that the π−π interaction and intermolecular hydrogen bonding are the major responsible factors for the self-assembled gelation process that are oriented through an antiparallel β-sheet arrangement of the peptide backbone. These Fmoc-based cationic molecules exhibited efficient antibacterial activity against both Gram-positive and Gram-negative bacteria.
Abstract
Nanomotor chassis constructed from biological precursors and powered by biocatalytic transformations can offer important applications in the future, specifically in emergent biomedical ...techniques. Herein, cross β amyloid peptide-based nanomotors (amylobots) were prepared from short amyloid peptides. Owing to their remarkable binding capabilities, these soft constructs are able to host dedicated enzymes to catalyze orthogonal substrates for motility and navigation. Urease helps in powering the self-diffusiophoretic motion, while cytochrome C helps in providing navigation control. Supported by the simulation model, the design principle demonstrates the utilization of two distinct transport behaviours for two different types of enzymes, firstly enhanced diffusivity of urease with increasing fuel (urea) concentration and secondly, chemotactic motility of cytochrome C towards its substrate (pyrogallol). Dual catalytic engines allow the amylobots to be utilized for enhanced catalysis in organic solvent and can thus complement the technological applications of enzymes.
In the present work, we report the superior activity of hydrophobically adsorbed enzymes onto single-walled carbon nanotubes (SWNTs) in the reverse micelles of cationic surfactants. Horseradish ...peroxidase and soybean peroxidase adsorbed onto SWNTs endure a notable loss in secondary structure and catalytic activity. This structurally and functionally deformed enzyme−SWNT when confined in CTAB reverse micelles showed ∼7−9-fold enhancement in activity compared to that was in water and also importantly ∼1500−3500 times higher activity than that of the enzymes in aqueous−organic biphasic mixtures. The activation observed for this nanobiocomposite is due to the (i) possible localization of enzyme−SWNT hybrid at the micellar interface; (ii) facile transport of substrates across the microscopic interface of reverse micelles; and (iii) greater local concentration of substrates at the augmented interfacial space in the presence of SWNT. This interfacial localization of the SWNT−protein hybrid was tested using FITC-tagged protein (BSA) by fluorescence spectroscopy. FTIR and CD spectroscopy established that the enzyme notably loses its native structure as it gets adsorbed onto the CNTs. However, this loss in the secondary structure is neither aggravated nor recovered when the enzyme-SWNT resides at the reverse micellar interface. So, localization of the surface-active peroxidase−CNT hybrids at the interface is the main reason for significant enzyme activation. The generality of the activation of the enzyme−CNT hybrid by reverse micelles was tested using amphiphiles with varying headgroup sizes, where an overall enhancement in activity was observed with an increase in headgroup size. Activation of this nanobiocomposite would find utmost importance in material science as the activity of structurally deprived enzyme in reverse micelles surpassed (∼1.7-fold) even the activity of the native enzyme in water.
.
We study the flocking model introduced by Vicsek
et al.
(Phys. Rev. Lett.
75
, 1226 (1995)) in the “coarsening” regime. At standard self-propulsion speeds, we find two distinct growth laws for the ...coupled density and velocity fields. The characteristic length scale of the density domains grows as
L
ρ
(
t
)
∼
t
θ
ρ
(with
θ
ρ
≃
0
.
25
, while the velocity length scale grows much faster,
viz.
,
L
v
(
t
)
∼
t
θ
v
(with
θ
v
≃
0
.
83
. The spatial fluctuations in the density and velocity fields are studied by calculating the two-point correlation function and the structure factor, which show deviations from the well-known Porod’s law. This is a natural consequence of scattering from irregular morphologies that dynamically arise in the system. At large values of the scaled wave vector, the scaled structure factors for the density and velocity fields decay with powers -2.6 and -1.52 , respectively.
Graphical abstract
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