Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Turn and Face the Strange: A New View on Phosphatases.

ABSTRACT: Phosphorylation as a post-translational modification is critical for cellular homeostasis. Kinases and phosphatases regulate phosphorylation levels by adding or removing, respectively, a phosphate group from proteins or other biomolecules. Imbalances in phosphorylation levels are involved in a multitude of diseases. Phosphatases are often thought of as the black sheep, the strangers, of phosphorylation-mediated signal transduction, particularly when it comes to drug discovery and development. This is due to past difficulties to study them and unsuccessful attempts to target them; however, phosphatases have regained strong attention and are actively pursued now in clinical trials. By giving examples for current hot topics in phosphatase biology and for new approaches to target them, it is illustrated here how and why phosphatases made their comeback, and what is envisioned to come in the future.

SUBMITTER: Kohn M

PROVIDER: S-EPMC7181316 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Turn and Face the Strange: A New View on Phosphatases.

Köhn Maja M

ACS central science 20200313 4

Phosphorylation as a post-translational modification is critical for cellular homeostasis. Kinases and phosphatases regulate phosphorylation levels by adding or removing, respectively, a phosphate group from proteins or other biomolecules. Imbalances in phosphorylation levels are involved in a multitude of diseases. Phosphatases are often thought of as the black sheep, the strangers, of phosphorylation-mediated signal transduction, particularly when it comes to drug discovery and development. Th ...[more]

PMID: 32341996

Similar Datasets

A systems view of mother-infant face-to-face communication.

Project description:Principles of a dynamic, dyadic systems view of mother-infant face-to-face communication, which considers self- and interactive processes in relation to one another, were tested. The process of interaction across time in a large low-risk community sample at infant age 4 months was examined. Split-screen videotape was coded on a 1-s time base for communication modalities of attention, affect, orientation, touch, and composite facial-visual engagement. Time-series approaches generated self- and interactive contingency estimates in each modality. Evidence supporting the following principles was obtained: (a) Significant moment-to-moment predictability within each partner (self-contingency) and between the partners (interactive contingency) characterizes mother-infant communication. (b) Interactive contingency is organized by a bidirectional, but asymmetrical, process: Maternal contingent coordination with infant is higher than infant contingent coordination with mother. (c) Self-contingency organizes communication to a far greater extent than interactive contingency. (d) Self- and interactive contingency processes are not separate; each affects the other in communication modalities of facial affect, facial-visual engagement, and orientation. Each person's self-organization exists in a dynamic, homoeostatic (negative feedback) balance with the degree to which the person coordinates with the partner. For example, those individuals who are less facially stable are likely to coordinate more strongly with the partner's facial affect and vice versa. Our findings support the concept that the dyad is a fundamental unit of analysis in the investigation of early interaction. Moreover, an individual's self-contingency is influenced by the way the individual coordinates with the partner. Our results imply that it is not appropriate to conceptualize interactive processes without simultaneously accounting for dynamically interrelated self-organizing processes.

| S-EPMC4808406 | biostudies-literature

Panoramic view of a superfamily of phosphatases through substrate profiling.

Project description:Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified iso-functional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process.

| S-EPMC4413258 | biostudies-literature

Signalling by protein phosphatases and drug development: a systems-centred view.

Project description:Protein modification cycles catalysed by opposing enzymes, such as kinases and phosphatases, form the backbone of signalling networks. Although, historically, kinases have been at the research forefront, a systems-centred approach reveals predominant roles for phosphatases in controlling the network response times and spatio-temporal profiles of signalling activities. Emerging evidence suggests that phosphatase kinetics are critical for network function and cell-fate decisions. Protein phosphatases operate as both immediate and delayed regulators of signal transduction, capable of attenuating or amplifying signalling. This versatility of phosphatase action emphasizes the need for systems biology approaches to understand cellular signalling networks and predict the cellular outcomes of combinatorial drug interventions.

| S-EPMC3368988 | biostudies-literature

View-tuned and view-invariant face encoding in IT cortex is explained by selected natural image fragments.

Project description:Humans recognize individual faces regardless of variation in the facial view. The view-tuned face neurons in the inferior temporal (IT) cortex are regarded as the neural substrate for view-invariant face recognition. This study approximated visual features encoded by these neurons as combinations of local orientations and colors, originated from natural image fragments. The resultant features reproduced the preference of these neurons to particular facial views. We also found that faces of one identity were separable from the faces of other identities in a space where each axis represented one of these features. These results suggested that view-invariant face representation was established by combining view sensitive visual features. The face representation with these features suggested that, with respect to view-invariant face representation, the seemingly complex and deeply layered ventral visual pathway can be approximated via a shallow network, comprised of layers of low-level processing for local orientations and colors (V1/V2-level) and the layers which detect particular sets of low-level elements derived from natural image fragments (IT-level).

| S-EPMC8035202 | biostudies-literature

Own-race and own-species advantages in face perception: a computational view.

Project description:The frequency to which an organism is exposed to a particular type of face influences recognition performance. For example, Asians are better in individuating Asian than Caucasian faces, known as the own-race advantage. Similarly, humans in general are better in individuating human than monkey faces, known as the own-species advantage. It is an open question whether the underlying mechanisms causing these effects are similar. We hypothesize that these processes are governed by neural plasticity of the face discrimination system to retain optimal discrimination performance in its environment. Using common face features derived from a set of images from various face classes, we show that maximizing the feature variance between different individuals while ensuring minimal variance within individuals achieved good discrimination performances on own-class faces when selecting a subset of feature dimensions. Further, the selected subset of features does not necessarily lead to an optimal performance on the other class of faces. Thus, the face discrimination system continuously re-optimizes its space constraint face representation to optimize recognition performance on the current distribution of faces in its environment. This model can account for both, the own-race and own-species advantages. We name this approach Space Constraint Optimized Representational Embedding (SCORE).

| S-EPMC4200398 | biostudies-other

The double lives of phosphatases of regenerating liver: A structural view of their catalytic and noncatalytic activities.

Project description:Phosphatases of regenerating liver (PRLs) are protein phosphatases involved in the control of cell growth and migration. They are known to promote cancer metastasis but, despite over 20 years of study, there is still no consensus about their mechanism of action. Recent work has revealed that PRLs lead double lives, acting both as catalytically active enzymes and as pseudophosphatases. The three known PRLs belong to the large family of cysteine phosphatases that form a phosphocysteine intermediate during catalysis. Uniquely to PRLs, this intermediate is stable, with a lifetime measured in hours. As a consequence, PRLs have very little phosphatase activity. Independently, PRLs also act as pseudophosphatases by binding CNNM membrane proteins to regulate magnesium homeostasis. In this function, an aspartic acid from CNNM inserts into the phosphatase catalytic site of PRLs, mimicking a substrate-enzyme interaction. The delineation of PRL pseudophosphatase and phosphatase activities in vivo was impossible until the recent identification of PRL mutants defective in one activity or the other. These mutants showed that CNNM binding was sufficient for PRL oncogenicity in one model of metastasis, but left unresolved its role in other contexts. As the presence of phosphocysteine prevents CNNM binding and CNNM-binding blocks catalytic activity, these two activities are inherently linked. Additional studies are needed to untangle the intertwined catalytic and noncatalytic functions of PRLs. Here, we review the current understanding of the structure and biophysical properties of PRL phosphatases.

| S-EPMC8728433 | biostudies-literature

The strange case of the earliest silver extraction by European colonists in the New World.

Project description:La Isabela, the first European town in the New World, was established in 1494 by the second expedition of Christopher Columbus but was abandoned by 1498. The main motive for settlement was to find and exploit deposits of precious metals. Archaeological evidence of silver extraction at La Isabela seemed to indicate that the expedition had located and tested deposits of silver-bearing lead ore in the Caribbean. Lead isotope analysis refutes this hypothesis but provides new evidence of the desperation of the inhabitants of La Isabela just before its abandonment.

| S-EPMC1805524 | biostudies-literature

A new view on crystal harvesting.

Project description:X-ray crystallography typically requires the mounting of crystals, which can make the sample difficult to manipulate when it is small and the microscope objective is close to the crystallization plate. By simply moving the objective to the bottom of a clear crystallization plate (inverting the normal view), crystals were able to be manipulated and harvested from wells having a 0.9 mm diameter and 5.0 mm depth. The mounting system enabled the structural solution of the 187 amino acid N-terminal domain of Saccharomyces cerevisiae glutaminyl-tRNA synthetase from crystals that appeared during high-throughput screening but proved recalcitrant to scale-up and optimization. While not a general mounting solution, the simple expedient of removing the objective lens from the area where manipulation and harvesting occur greatly facilitates the manual, or even automated, process.

| S-EPMC4038804 | biostudies-literature

Disentangling the Representation of Identity from Head View Along the Human Face Processing Pathway.

Project description:Neural models of a distributed system for face perception implicate a network of regions in the ventral visual stream for recognition of identity. Here, we report a functional magnetic resonance imaging (fMRI) neural decoding study in humans that shows that this pathway culminates in the right inferior frontal cortex face area (rIFFA) with a representation of individual identities that has been disentangled from variable visual features in different images of the same person. At earlier stages in the pathway, processing begins in early visual cortex and the occipital face area with representations of head view that are invariant across identities, and proceeds to an intermediate level of representation in the fusiform face area in which identity is emerging but still entangled with head view. Three-dimensional, view-invariant representation of identities in the rIFFA may be the critical link to the extended system for face perception, affording activation of person knowledge and emotional responses to familiar faces.

| S-EPMC5939212 | biostudies-literature

The kink-turn: a new RNA secondary structure motif.

Project description:Analysis of the Haloarcula marismortui large ribosomal subunit has revealed a common RNA structure that we call the kink-turn, or K-turn. The six K-turns in H.marismortui 23S rRNA superimpose with an r.m.s.d. of 1.7 A. There are two K-turns in the structure of Thermus thermophilus 16S rRNA, and the structures of U4 snRNA and L30e mRNA fragments form K-turns. The structure has a kink in the phosphodiester backbone that causes a sharp turn in the RNA helix. Its asymmetric internal loop is flanked by C-G base pairs on one side and sheared G-A base pairs on the other, with an A-minor interaction between these two helical stems. A derived consensus secondary structure for the K-turn includes 10 consensus nucleotides out of 15, and predicts its presence in the 5'-UTR of L10 mRNA, helix 78 in Escherichia coli 23S rRNA and human RNase MRP. Five K-turns in 23S rRNA interact with nine proteins. While the observed K-turns interact with proteins of unrelated structures in different ways, they interact with L7Ae and two homologous proteins in the same way.

| S-EPMC149158 | 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