Goals and Challenges in Bacterial Phosphoproteomics DOI Open Access
Paula Yagüe, Nathaly González-Quiñónez, Gemma Fernández-García

et al.

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(22), P. 5678 - 5678

Published: Nov. 13, 2019

Reversible protein phosphorylation at serine, threonine and tyrosine is a well-known dynamic post-translational modification with stunning regulatory signalling functions in eukaryotes. Shotgun phosphoproteomic analyses revealed that this dramatically lower bacteria than However, Ser/Thr/Tyr present all analysed (24 eubacteria 1 archaea). It affects central processes, such as primary secondary metabolism development, sporulation, pathogenicity, virulence or antibiotic resistance. Twenty-nine phosphoprotein orthologues were systematically identified bacteria: ribosomal proteins, enzymes from glycolysis gluconeogenesis, elongation factors, cell division RNA polymerases, ATP synthases the citrate cycle. While exists bacteria, there consensus histidine most abundant prokaryotes. Unfortunately, shotgun phosphorproteomics not possible due to reduced phosphohistidine half-life under acidic pH conditions used standard LC-MS/MS analysis. considering fast continuous advances LC-MS/MS-based methodologies, it expected further innovations will allow for study of His phosphoproteomes better coverage bacterial phosphoproteomes. The characterisation biological role phosphorylations might revolutionise our understanding prokaryotic physiology.

Language: Английский

Subtractive genomics profiling for potential drug targets identification against Moraxella catarrhalis DOI Creative Commons
Bilal Ashraf,

Nimrah Atiq,

Kanwal Khan

et al.

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(8), P. e0273252 - e0273252

Published: Aug. 25, 2022

Moraxella catarrhalis (M . ) is a gram-negative bacterium, responsible for major respiratory tract and middle ear infection in infants adults. The recent emergence of the antibiotic resistance M demands prioritization an effective drug target as top priority. Fortunately, failure new drugs host toxicity associated with traditional development approaches can be avoided by using silico subtractive genomics approach. In current study, advanced genome subtraction approach was applied to identify potential pathogen-specific targets against We series methods from whole pathogen based on certain steps i.e. paralogous protein that have extensive homology humans, essential, like, non-virulent, resistant proteins. Only 38 potent were identified this study. Eventually, one forwarded structure-based studies histidine kinase (UniProt ID: D5VAF6). Furthermore, virtual screening 2000 compounds ZINC database performed resulted shortlisting three therapeutic candidates their binding energies properties exhibited ADMET analysis. gives platform discovery lead candidate may inhibit it help eradicate otitis media caused drug-resistant Nevertheless, study helped creating pipeline identification assist wet-lab research future.

Language: Английский

Citations

25
Comparative Metabolic Pathways Analysis and Subtractive Genomics Profiling to Prioritize Potential Drug Targets Against Streptococcus pneumoniae DOI Creative Commons

Kanwal Khan,

Khurshid Jalal, Ajmal Khan

et al.

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Feb. 10, 2022

Graphical Abstract

Language: Английский

Citations

24
Light-regulated gene expression in Bacteria: Fundamentals, advances, and perspectives DOI Creative Commons
Robert Ohlendorf, Andreas Möglich

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 14, 2022

Numerous photoreceptors and genetic circuits emerged over the past two decades now enable light-dependent i.e., optogenetic, regulation of gene expression in bacteria. Prompted by light cues near-ultraviolet to near-infrared region electromagnetic spectrum, can be up- or downregulated stringently, reversibly, non-invasively, with precision space time. Here, we survey underlying principles, available options, prominent examples optogenetically regulated While transcription initiation elongation remain most important for optogenetic intervention, other processes e.g., translation downstream events, were also rendered light-dependent. The control bacterial predominantly employs but three fundamental strategies: light-sensitive two-component systems, oligomerization reactions, second-messenger signaling. Certain moved beyond proof-of-principle stood test practice. They unprecedented applications major areas. First, underpins novel concepts strategies enhanced yields microbial production processes. Second, light-responsive bacteria stimulated while residing within bodies animals, thus prompting secretion compounds that grant health benefits animal host. Third, optogenetics allows generation precisely structured, biomaterials. These jointly testify maturity approach serve as blueprints bound inspire template innovative use cases light-regulated Researchers pursuing these lines choose from an ever-growing, versatile, efficient toolkit circuits.

Language: Английский

Citations

24
Navigating the signaling landscape of Ralstonia solanacearum: a study of bacterial two-component systems DOI
Mohit Yadav,

Janhavi Sathe,

Valentina Teronpi

et al.

World Journal of Microbiology and Biotechnology, Journal Year: 2024, Volume and Issue: 40(5)

Published: April 2, 2024

Language: Английский

Citations

5
Optogenetic Control of Bacterial Expression by Red Light DOI Creative Commons
Elina Multamäki, Andrés García de Fuentes, Oleksii Sieryi

et al.

ACS Synthetic Biology, Journal Year: 2022, Volume and Issue: 11(10), P. 3354 - 3367

Published: Aug. 23, 2022

In optogenetics, as in nature, sensory photoreceptors serve to control cellular processes by light. Bacteriophytochrome (BphP) sense red and far-red light via a biliverdin chromophore and, response, cycle between the spectroscopically, structurally, functionally distinct Pr Pfr states. BphPs commonly belong two-component systems that phosphorylation of cognate response regulators downstream gene expression through histidine kinase modules. We recently demonstrated paradigm BphP from

Language: Английский

Citations

22
Light-Oxygen-Voltage (LOV)-sensing Domains: Activation Mechanism and Optogenetic Stimulation DOI Creative Commons
Andrea Flores-Ibarra,

Raiza N.A. Maia,

Bence Olasz

et al.

Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 436(5), P. 168356 - 168356

Published: Nov. 7, 2023

The light-oxygen-voltage (LOV) domains of phototropins emerged as essential constituents light-sensitive proteins, helping initiate blue light-triggered responses. Moreover, these have been identified across all kingdoms life. LOV utilize flavin nucleotides co-factors and undergo structural rearrangements upon exposure to light, which activates an effector domain that executes the final output photoreaction. are versatile photoreceptors play critical roles in cellular signaling environmental adaptation; additionally, they can noninvasively sense control intracellular processes with high spatiotemporal precision, making them ideal candidates for use optogenetics, where a light signal is linked process through photoreceptor. ongoing development LOV-based optogenetic tools, driven by advances biology, spectroscopy, computational methods, synthetic has potential revolutionize study biological systems enable novel therapeutic strategies.

Language: Английский

Citations

11
Refolding of the Deinococcus Radiodurans phytochrome photosensory module and an extended backbone resonance assignment by solution NMR DOI Creative Commons
Lidija Vrhovac, Maria Levkovets, Vladislav Orekhov

et al.

Protein Expression and Purification, Journal Year: 2025, Volume and Issue: unknown, P. 106699 - 106699

Published: March 1, 2025

Solution NMR reveals the structure and dynamics of biomolecules in solution. In particular, method can detect changes due to perturbation molecules, without limiting effects frozen particles or crystal environments. Phytochromes are photosensors which control response red/far-red light bacteria, fungi plants, undergo specific structural when photoactivated from Pr Pfr state. While structures phytochromes have been revealed both states, mechanism photoconversion remains incompletely understood. Our previous studies entire photosensory core module D. radiodurans phytochrome novel changes, but backbone assignment was incomplete. a lack protein hindered more detailed insight signaling mechanism. Here, we outline an efficient procedure for refolding three-domain, fragment its monomeric form. We find that treatment with guanidinium hydrochloride subsequent dilution effectively refolds phytrochrome, maintaining functionality. characterize refolded solution spectroscopy newly assigning 27 (44) residues (Pfr), out 12 exhibit notable chemical shift upon photoactivation. The study presents functional purification multidomain opens door further dynamic analysis phytochromes. Author summary Refolding proteins is established increase deuterium-hydrogen exchange amid bonds isotopically labeled proteins, located deep core. Yet, has be optimized each individual particular it not trivial satisfactory experimental conditions. Here identify refold construct outcome using optical spectroscopy. quick accessibility on whether obtained spectra, also made screening number additives possible. led significant assigned especially core, close photochemically active chromophore, enables investigation throughout photocycle phytochrome.

Language: Английский

Citations

0
Lichtschalter zur Kontrolle bakterieller Transkription und Translation DOI Creative Commons
Marius Blackholm, Stefanie Meier, Andreas Möglich

et al.

BIOspektrum, Journal Year: 2025, Volume and Issue: 31(2), P. 154 - 157

Published: March 1, 2025

Language: Английский

Citations

0
Coevolving residues distant from the ligand binding site are involved in GAF domain function DOI Creative Commons
Wesam S. Ahmed,

Anupriya M. Geethakumari,

Asfia Sultana

et al.

Communications Chemistry, Journal Year: 2025, Volume and Issue: 8(1)

Published: April 7, 2025

Abstract Ligand binding to GAF domains regulates the activity of associated catalytic in various proteins, such as cGMP-hydrolyzing domain phosphodiesterase 5 (PDE5) activated by cGMP GAFa domain. However, specific residues involved and mechanism function remain unclear. Here, we combine computational experimental approaches demonstrate that two highly coevolving residues, L267 F295, distant from ligand site, play a critical role allostery. Statistical Coupling Analysis (SCA) sequences identified these molecular dynamics (MD) simulations both apo holo forms wild-type mutant (L267A, F295A) PDE5 revealed significant changes structural interaction. Mutational incorporation into Bioluminescence Resonance Energy Transfer (BRET)-based biosensors, which detects ligand-induced conformational changes, showed altered conformation increased EC 50 for cGMP-induced changes. Similar effects were observed full-length fluorescent protein, miRFP670nano3. Structural analysis conformers MD suggested influence Our findings provide insight may enhance understanding allostery proteins.

Language: Английский

Citations

0
Variations in kinase and effector signaling logic in a bacterial two component signaling network DOI Creative Commons
Danielle Swingle, Lois B. Epstein, Ramisha Aymon

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108534 - 108534

Published: April 1, 2025

Language: Английский

Citations

0