Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The ascent of man(made oxidoreductases).

ABSTRACT: Though established 40 years ago, the field of de novo protein design has recently come of age, with new designs exhibiting an unprecedented level of sophistication in structure and function. With respect to catalysis, de novo enzymes promise to revolutionise the industrial production of useful chemicals and materials, while providing new biomolecules as plug-and-play components in the metabolic pathways of living cells. To this end, there are now de novo metalloenzymes that are assembled in vivo, including the recently reported C45 maquette, which can catalyse a variety of substrate oxidations with efficiencies rivalling those of closely related natural enzymes. Here we explore the successful design of this de novo enzyme, which was designed to minimise the undesirable complexity of natural proteins using a minimalistic bottom-up approach.

SUBMITTER: Grayson KJ

PROVIDER: S-EPMC6227378 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The ascent of man(made oxidoreductases).

Grayson Katie J KJ Anderson Jl Ross JR

Current opinion in structural biology 20180510

Though established 40 years ago, the field of de novo protein design has recently come of age, with new designs exhibiting an unprecedented level of sophistication in structure and function. With respect to catalysis, de novo enzymes promise to revolutionise the industrial production of useful chemicals and materials, while providing new biomolecules as plug-and-play components in the metabolic pathways of living cells. To this end, there are now de novo metalloenzymes that are assembled in vivo ...[more]

PMID: 29754103

Similar Datasets

Man made deltas.

Project description:The review of geochronological and historical data documents that the largest southern European deltas formed almost synchronously during two short intervals of enhanced anthropic pressure on landscapes, respectively during the Roman Empire and the Little Ice Age. These growth phases, that occurred under contrasting climatic regimes, were both followed by generalized delta retreat, driven by two markedly different reasons: after the Romans, the fall of the population and new afforestation let soil erosion in river catchments return to natural background levels; since the industrial revolution, instead, flow regulation through river dams overkill a still increasing sediment production in catchment basins. In this second case, furthermore, the effect of a reduced sediment flux to the coasts is amplified by the sinking of modern deltas, due to land subsidence and sea level rise, that hampers delta outbuilding and increases the vulnerability of coastal zone to marine erosion and flooding.

| S-EPMC3668317 | biostudies-literature

Man-made microbial resistances in built environments.

Project description:Antimicrobial resistance is a serious threat to global public health, but little is known about the effects of microbial control on the microbiota and its associated resistome. Here we compare the microbiota present on surfaces of clinical settings with other built environments. Using state-of-the-art metagenomics approaches and genome and plasmid reconstruction, we show that increased confinement and cleaning is associated with a loss of microbial diversity and a shift from Gram-positive bacteria, such as Actinobacteria and Firmicutes, to Gram-negative such as Proteobacteria. Moreover, the microbiome of highly maintained built environments has a different resistome when compared to other built environments, as well as a higher diversity in resistance genes. Our results highlight that the loss of microbial diversity correlates with an increase in resistance, and the need for implementing strategies to restore bacterial diversity in certain built environments.

| S-EPMC6393488 | biostudies-literature

Natural and Man-Made Cyclic Peptide-Based Antibiotics.

Project description:In recent years, an increasing number of drug-resistant bacterial strains have been identified due to the abuse of antibiotics, which seriously threatens human and animal health. Antimicrobial peptides (AMPs) have become one of the most effective weapons to solve this problem. AMPs have little tendency to induce drug resistance and have outstanding antimicrobial effects. The study of AMPs, especially cyclic peptides, has become a hot topic. Among them, macrocyclic AMPs have received extensive attention. This mini-review discusses the structures and functions of the dominant cyclic natural and synthetic AMPs and provides a little outlook on the future direction of cyclic AMPs.

| S-EPMC9855121 | biostudies-literature

A perceptual bias for man-made objects in humans.

Project description:Ambiguous images are widely recognized as a valuable tool for probing human perception. Perceptual biases that arise when people make judgements about ambiguous images reveal their expectations about the environment. While perceptual biases in early visual processing have been well established, their existence in higher-level vision has been explored only for faces, which may be processed differently from other objects. Here we developed a new, highly versatile method of creating ambiguous hybrid images comprising two component objects belonging to distinct categories. We used these hybrids to measure perceptual biases in object classification and found that images of man-made (manufactured) objects dominated those of naturally occurring (non-man-made) ones in hybrids. This dominance generalized to a broad range of object categories, persisted when the horizontal and vertical elements that dominate man-made objects were removed and increased with the real-world size of the manufactured object. Our findings show for the first time that people have perceptual biases to see man-made objects and suggest that extended exposure to manufactured environments in our urban-living participants has changed the way that they see the world.

| S-EPMC6842849 | biostudies-literature

Man-made microbial resistances in built environments

Project description:Comparative metagenomics of controlled and uncontrolled built environments.

| PRJEB27640 | ENA

Natural and man-made V-gene repertoires for antibody discovery.

Project description:Antibodies are the fastest-growing segment of the biologics market. The success of antibody-based drugs resides in their exquisite specificity, high potency, stability, solubility, safety, and relatively inexpensive manufacturing process in comparison with other biologics. We outline here the structural studies and fundamental principles that define how antibodies interact with diverse targets. We also describe the antibody repertoires and affinity maturation mechanisms of humans, mice, and chickens, plus the use of novel single-domain antibodies in camelids and sharks. These species all utilize diverse evolutionary solutions to generate specific and high affinity antibodies and illustrate the plasticity of natural antibody repertoires. In addition, we discuss the multiple variations of man-made antibody repertoires designed and validated in the last two decades, which have served as tools to explore how the size, diversity, and composition of a repertoire impact the antibody discovery process.

| S-EPMC3498902 | biostudies-literature

Engineering the assembly of heme cofactors in man-made proteins.

Project description:Timely ligation of one or more chemical cofactors at preselected locations in proteins is a critical preamble for catalysis in many natural enzymes, including the oxidoreductases and allied transport and signaling proteins. Likewise, ligation strategies must be directly addressed when designing oxidoreductase and molecular transport functions in man-made, first-principle protein constructs intended to operate in vitro or in vivo. As one of the most common catalytic cofactors in biology, we have chosen heme B, along with its chemical analogues, to determine the kinetics and barriers to cofactor incorporation and bishistidine ligation in a range of 4-α-helix proteins. We compare five elementary synthetic designs (maquettes) and the natural cytochrome b562 that differ in oligomeric forms, apo- and holo-tertiary structural stability; qualities that we show can either assist or hinder assembly. The cofactor itself also imposes an assembly barrier if amphiphilicity ranges toward too hydrophobic or hydrophilic. With progressive removal of identified barriers, we achieve maquette assembly rates as fast as native cytochrome b562, paving the way to in vivo assembly of man-made hemoprotein maquettes and integration of artificial proteins into enzymatic pathways.

| S-EPMC3985801 | biostudies-literature

HPLC methods for purity evaluation of man-made single-stranded RNAs.

Project description:Synthetic RNA oligos exhibit purity decreasing as a function of length, because the efficiency of the total synthesis is the numerical product of the individual step efficiencies, typically below 98%. Analytical methods for RNAs up to the 60 nucleotides (nt) have been reported, but they fall short for purity evaluation of 100nt long, used as single guide RNA (sgRNA) in CRISPR technology, and promoted as pharmaceuticals. In an attempt to exploit a single HPLC method and obtain both identity as well as purity, ion-pair reversed-phase chromatography (IP-RP) at high temperature in the presence of an organic cosolvent is the current analytical strategy. Here we report that IP-RP is less suitable compared to the conventional ion-exchange (IEX) for analysis of 100nt RNAs. We demonstrate the relative stability of RNA in the denaturing/basic IEX mobile phase, lay out a protocol to determine the on-the-column stability of any RNA, and establish the applicability of this method for quality testing of sgRNA, tRNA, and mRNA. Unless well resolving HPLC methods are used for batch-to-batch evaluation of man-made RNAs, process development will remain shortsighted, and observed off-target effects in-vitro or in-vivo may be partially related to low purity and the presence of shorter sequences.

| S-EPMC6356003 | biostudies-literature

Design and engineering of a man-made diffusive electron-transport protein.

Project description:Maquettes are man-made cofactor-binding oxidoreductases designed from first principles with minimal reference to natural protein sequences. Here we focus on water-soluble maquettes designed and engineered to perform diffusive electron transport of the kind typically carried out by cytochromes, ferredoxins and flavodoxins and other small proteins in photosynthetic and respiratory energy conversion and oxido-reductive metabolism. Our designs were tested by analysis of electron transfer between heme maquettes and the well-known natural electron transporter, cytochrome c. Electron-transfer kinetics were measured from seconds to milliseconds by stopped-flow, while sub-millisecond resolution was achieved through laser photolysis of the carbon monoxide maquette heme complex. These measurements demonstrate electron transfer from the maquette to cytochrome c, reproducing the timescales and charge complementarity modulation observed in natural systems. The ionic strength dependence of inter-protein electron transfer from 9.7×10(6) M(-1) s(-1) to 1.2×10(9) M(-1) s(-1) follows a simple Debye-Hückel model for attraction between +8 net charged oxidized cytochrome c and -19 net charged heme maquette, with no indication of significant protein dipole moment steering. Successfully recreating essential components of energy conversion and downstream metabolism in man-made proteins holds promise for in vivo clinical intervention and for the production of fuel or other industrial products. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson.

| S-EPMC4910091 | biostudies-literature

Physics-based forecasting of man-made earthquake hazards in Oklahoma and Kansas.

Project description:Reinjection of saltwater, co-produced with oil, triggered thousands of widely felt and several damaging earthquakes in Oklahoma and Kansas. The future seismic hazard remains uncertain. Here, we present a new methodology to forecast the probability of damaging induced earthquakes in space and time. In our hybrid physical-statistical model, seismicity is driven by the rate of injection-induced pressure increases at any given location and spatial variations in the number and stress state of preexisting basement faults affected by the pressure increase. If current injection practices continue, earthquake hazards are expected to decrease slowly. Approximately 190, 130 and 100 widely felt M???3 earthquakes are anticipated in 2018, 2019 and 2020, respectively, with corresponding probabilities of potentially damaging M???5 earthquakes of 32, 24 and 19%. We identify areas where produced-water injection is more likely to cause seismicity. Our methodology can be used to evaluate future injection scenarios intended to mitigate seismic hazards.

| S-EPMC6158231 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data