LIVIVO - Search results -

Search results

Result 1 - 10 of total 32

Search options

Article ; Online: Sequence and Structure-Based Analysis of Specificity Determinants in Eukaryotic Protein Kinases.

Bradley, David / Viéitez, Cristina / Rajeeve, Vinothini / Selkrig, Joel / Cutillas, Pedro R / Beltrao, Pedro

2021 Volume 34, Issue 2, Page(s) 108602

Abstract: Protein kinases lie at the heart of cell-signaling processes and are often mutated in disease. Kinase target recognition at the active site is in part determined by a few amino acids around the phosphoacceptor residue. However, relatively little is known ...

Abstract	Protein kinases lie at the heart of cell-signaling processes and are often mutated in disease. Kinase target recognition at the active site is in part determined by a few amino acids around the phosphoacceptor residue. However, relatively little is known about how most preferences are encoded in the kinase sequence or how these preferences evolved. Here, we used alignment-based approaches to predict 30 specificity-determining residues (SDRs) for 16 preferences. These were studied with structural models and were validated by activity assays of mutant kinases. Cancer mutation data revealed that kinase SDRs are mutated more frequently than catalytic residues. We have observed that, throughout evolution, kinase specificity has been strongly conserved across orthologs but can diverge after gene duplication, as illustrated by the G protein-coupled receptor kinase family. The identified SDRs can be used to predict kinase specificity from sequence and aid in the interpretation of evolutionary or disease-related genomic variants.
MeSH term(s)	Animals ; Eukaryota/metabolism ; Humans ; Mice ; Models, Molecular ; Phosphorylation ; Protein Kinases/metabolism ; Protein Processing, Post-Translational/genetics ; Signal Transduction
Chemical Substances	Protein Kinases (EC 2.7.-)
Language	English
Publishing date	2021-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.108602
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article: Systematic Localization of Escherichia coli Membrane Proteins.

Sueki, Anna / Stein, Frank / Savitski, Mikhail M / Selkrig, Joel / Typas, Athanasios

mSystems

2020 Volume 5, Issue 2

Abstract: The molecular architecture and function of the Gram-negative bacterial cell envelope are dictated by protein composition and localization. Proteins that localize to the inner membranes (IM) and outer membranes (OM) of Gram-negative bacteria play critical ...

Abstract	The molecular architecture and function of the Gram-negative bacterial cell envelope are dictated by protein composition and localization. Proteins that localize to the inner membranes (IM) and outer membranes (OM) of Gram-negative bacteria play critical and distinct roles in cellular physiology; however, approaches to systematically interrogate their distribution across both membranes and the soluble cell fraction are lacking. Here, we employed multiplexed quantitative mass spectrometry using tandem mass tag (TMT) labeling to assess membrane protein localization in a proteome-wide fashion by separating IM and OM vesicles from exponentially growing
Language	English
Publishing date	2020-03-03
Publishing country	United States
Document type	Journal Article
ISSN	2379-5077
ISSN	2379-5077
DOI	10.1128/mSystems.00808-19
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Sequence and Structure-Based Analysis of Specificity Determinants in Eukaryotic Protein Kinases

David Bradley / Cristina Viéitez / Vinothini Rajeeve / Joel Selkrig / Pedro R. Cutillas / Pedro Beltrao

Cell Reports, Vol 34, Iss 2, Pp 108602- (2021)

2021

Abstract: Summary: Protein kinases lie at the heart of cell-signaling processes and are often mutated in disease. Kinase target recognition at the active site is in part determined by a few amino acids around the phosphoacceptor residue. However, relatively little ...

Abstract	Summary: Protein kinases lie at the heart of cell-signaling processes and are often mutated in disease. Kinase target recognition at the active site is in part determined by a few amino acids around the phosphoacceptor residue. However, relatively little is known about how most preferences are encoded in the kinase sequence or how these preferences evolved. Here, we used alignment-based approaches to predict 30 specificity-determining residues (SDRs) for 16 preferences. These were studied with structural models and were validated by activity assays of mutant kinases. Cancer mutation data revealed that kinase SDRs are mutated more frequently than catalytic residues. We have observed that, throughout evolution, kinase specificity has been strongly conserved across orthologs but can diverge after gene duplication, as illustrated by the G protein-coupled receptor kinase family. The identified SDRs can be used to predict kinase specificity from sequence and aid in the interpretation of evolutionary or disease-related genomic variants.
Keywords	kinase ; phosphorylation ; signaling ; protein evolution ; specificity-determining residues ; enzymes ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Correlative proteomics identify the key roles of stress tolerance strategies in Acinetobacter baumannii in response to polymyxin and human macrophages.

Kho, Zhi Ying / Azad, Mohammad A K / Han, Mei-Ling / Zhu, Yan / Huang, Cheng / Schittenhelm, Ralf B / Naderer, Thomas / Velkov, Tony / Selkrig, Joel / Zhou, Qi Tony / Li, Jian

PLoS pathogens

2022 Volume 18, Issue 3, Page(s) e1010308

Abstract: The opportunistic pathogen Acinetobacter baumannii possesses stress tolerance strategies against host innate immunity and antibiotic killing. However, how the host-pathogen-antibiotic interaction affects the overall molecular regulation of bacterial ... ...

Abstract	The opportunistic pathogen Acinetobacter baumannii possesses stress tolerance strategies against host innate immunity and antibiotic killing. However, how the host-pathogen-antibiotic interaction affects the overall molecular regulation of bacterial pathogenesis and host response remains unexplored. Here, we simultaneously investigate proteomic changes in A. baumannii and macrophages following infection in the absence or presence of the polymyxins. We discover that macrophages and polymyxins exhibit complementary effects to disarm several stress tolerance and survival strategies in A. baumannii, including oxidative stress resistance, copper tolerance, bacterial iron acquisition and stringent response regulation systems. Using the spoT mutant strains, we demonstrate that bacterial cells with defects in stringent response exhibit enhanced susceptibility to polymyxin killing and reduced survival in infected mice, compared to the wild-type strain. Together, our findings highlight that better understanding of host-pathogen-antibiotic interplay is critical for optimization of antibiotic use in patients and the discovery of new antimicrobial strategy to tackle multidrug-resistant bacterial infections.
MeSH term(s)	Acinetobacter Infections/drug therapy ; Acinetobacter Infections/microbiology ; Acinetobacter baumannii ; Animals ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Multiple, Bacterial ; Humans ; Macrophages ; Mice ; Microbial Sensitivity Tests ; Polymyxins/pharmacology ; Proteomics
Chemical Substances	Anti-Bacterial Agents ; Polymyxins
Language	English
Publishing date	2022-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010308
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Metabolic tinkering by the gut microbiome: Implications for brain development and function.

Selkrig, Joel / Wong, Peiyan / Zhang, Xiaodong / Pettersson, Sven

Gut microbes

2014 Volume 5, Issue 3, Page(s) 369–380

Abstract: Brain development is an energy demanding process that relies heavily upon diet derived nutrients. Gut microbiota enhance the host's ability to extract otherwise inaccessible energy from the diet via fermentation of complex oligosaccharides in the colon. ... ...

Abstract	Brain development is an energy demanding process that relies heavily upon diet derived nutrients. Gut microbiota enhance the host's ability to extract otherwise inaccessible energy from the diet via fermentation of complex oligosaccharides in the colon. This nutrient yield is estimated to contribute up to 10% of the host's daily caloric requirement in humans and fluctuates in response to environmental variations. Research over the past decade has demonstrated a surprising role for the gut microbiome in normal brain development and function. In this review we postulate that perturbations in the gut microbial-derived nutrient supply, driven by environmental variation, profoundly impacts upon normal brain development and function.
MeSH term(s)	Brain/drug effects ; Brain/growth & development ; Food ; Gastrointestinal Tract/microbiology ; Humans ; Metabolism ; Microbiota
Language	English
Publishing date	2014-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1949-0984
ISSN (online)	1949-0984
DOI	10.4161/gmic.28681
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Systematic analysis of drug combinations against Gram-positive bacteria.

Nature microbiology

2023 Volume 8, Issue 11, Page(s) 2196–2212

Abstract: Drug combinations can expand options for antibacterial therapies but have not been systematically tested in Gram-positive species. We profiled ~8,000 combinations of 65 antibacterial drugs against the model species Bacillus subtilis and two prominent ... ...

Abstract	Drug combinations can expand options for antibacterial therapies but have not been systematically tested in Gram-positive species. We profiled ~8,000 combinations of 65 antibacterial drugs against the model species Bacillus subtilis and two prominent pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Thereby, we recapitulated previously known drug interactions, but also identified ten times more novel interactions in the pathogen S. aureus, including 150 synergies. We showed that two synergies were equally effective against multidrug-resistant S. aureus clinical isolates in vitro and in vivo. Interactions were largely species-specific and synergies were distinct from those of Gram-negative species, owing to cell surface and drug uptake differences. We also tested 2,728 combinations of 44 commonly prescribed non-antibiotic drugs with 62 drugs with antibacterial activity against S. aureus and identified numerous antagonisms that might compromise the efficacy of antimicrobial therapies. We identified even more synergies and showed that the anti-aggregant ticagrelor synergized with cationic antibiotics by modifying the surface charge of S. aureus. All data can be browsed in an interactive interface ( https://apps.embl.de/combact/ ).
MeSH term(s)	Staphylococcus aureus ; Methicillin-Resistant Staphylococcus aureus ; Anti-Bacterial Agents/pharmacology ; Gram-Positive Bacteria ; Drug Combinations
Chemical Substances	Anti-Bacterial Agents ; Drug Combinations
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Journal Article
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-023-01486-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Correlative proteomics identify the key roles of stress tolerance strategies in Acinetobacter baumannii in response to polymyxin and human macrophages.

Zhi Ying Kho / Mohammad A K Azad / Mei-Ling Han / Yan Zhu / Cheng Huang / Ralf B Schittenhelm / Thomas Naderer / Tony Velkov / Joel Selkrig / Qi Tony Zhou / Jian Li

PLoS Pathogens, Vol 18, Iss 3, p e

2022 Volume 1010308

Abstract	The opportunistic pathogen Acinetobacter baumannii possesses stress tolerance strategies against host innate immunity and antibiotic killing. However, how the host-pathogen-antibiotic interaction affects the overall molecular regulation of bacterial pathogenesis and host response remains unexplored. Here, we simultaneously investigate proteomic changes in A. baumannii and macrophages following infection in the absence or presence of the polymyxins. We discover that macrophages and polymyxins exhibit complementary effects to disarm several stress tolerance and survival strategies in A. baumannii, including oxidative stress resistance, copper tolerance, bacterial iron acquisition and stringent response regulation systems. Using the spoT mutant strains, we demonstrate that bacterial cells with defects in stringent response exhibit enhanced susceptibility to polymyxin killing and reduced survival in infected mice, compared to the wild-type strain. Together, our findings highlight that better understanding of host-pathogen-antibiotic interplay is critical for optimization of antibiotic use in patients and the discovery of new antimicrobial strategy to tackle multidrug-resistant bacterial infections.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Correlative proteomics identify the key roles of stress tolerance strategies in Acinetobacter baumannii in response to polymyxin and human macrophages

Zhi Ying Kho / Mohammad A. K. Azad / Mei-Ling Han / Yan Zhu / Cheng Huang / Ralf B. Schittenhelm / Thomas Naderer / Tony Velkov / Joel Selkrig / Qi (Tony) Zhou / Jian Li

PLoS Pathogens, Vol 18, Iss

2022 Volume 3

Abstract	The opportunistic pathogen Acinetobacter baumannii possesses stress tolerance strategies against host innate immunity and antibiotic killing. However, how the host-pathogen-antibiotic interaction affects the overall molecular regulation of bacterial pathogenesis and host response remains unexplored. Here, we simultaneously investigate proteomic changes in A. baumannii and macrophages following infection in the absence or presence of the polymyxins. We discover that macrophages and polymyxins exhibit complementary effects to disarm several stress tolerance and survival strategies in A. baumannii, including oxidative stress resistance, copper tolerance, bacterial iron acquisition and stringent response regulation systems. Using the spoT mutant strains, we demonstrate that bacterial cells with defects in stringent response exhibit enhanced susceptibility to polymyxin killing and reduced survival in infected mice, compared to the wild-type strain. Together, our findings highlight that better understanding of host-pathogen-antibiotic interplay is critical for optimization of antibiotic use in patients and the discovery of new antimicrobial strategy to tackle multidrug-resistant bacterial infections. Author summary Bacterial response towards antibiotics is sensitive to the surrounding environment; however, how the host immune microenvironment affects the response of opportunistic pathogen Acinetobacter baumannii towards polymyxins remains largely unexplored. In this study, we established a host-pathogen-antibiotic tripartite in vitro model to examine the complex tripartite molecular interplay from both bacteria and macrophages perspectives, mimicking the physiological infection-treatment condition. This is the first comprehensive proteomics dataset for A. baumannii interacting with host cells, with an extraordinary coverage (i.e., 50%) of A. baumannii proteome even in infection conditions. For the first time, we report that macrophages and polymyxins utilize complementary mechanisms to disarm several A. baumannii stress tolerance strategies to persist in the macrophages. Our host-pathogen-antibiotic mechanistic study and the discovery of potential druggable targets (e.g., bacterial stringent stress response regulator SpoT) represent a significant advance, paving way to antibiotic optimization and drug discovery to tackle multidrug-resistant bacterial infections.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Evolution of the Translocation and Assembly Module (TAM).

Heinz, Eva / Selkrig, Joel / Belousoff, Matthew J / Lithgow, Trevor

Genome biology and evolution

2015 Volume 7, Issue 6, Page(s) 1628–1643

Abstract: Bacterial outer membrane proteins require the beta-barrel assembly machinery (BAM) for their correct folding and function. The central component of this machinery is BamA, an Omp85 protein that is essential and found in all Gram-negative bacteria. An ... ...

Abstract	Bacterial outer membrane proteins require the beta-barrel assembly machinery (BAM) for their correct folding and function. The central component of this machinery is BamA, an Omp85 protein that is essential and found in all Gram-negative bacteria. An additional feature of the BAM is the translocation and assembly module (TAM), comprised TamA (an Omp85 family protein) and TamB. We report that TamA and a closely related protein TamL are confined almost exclusively to Proteobacteria and Bacteroidetes/Chlorobi respectively, whereas TamB is widely distributed across the majority of Gram-negative bacterial lineages. A comprehensive phylogenetic and secondary structure analysis of the TamB protein family revealed that TamB was present very early in the evolution of bacteria. Several sequence characteristics were discovered to define the TamB protein family: A signal-anchor linkage to the inner membrane, beta-helical structure, conserved domain architecture and a C-terminal region that mimics outer membrane protein beta-strands. Taken together, the structural and phylogenetic analyses suggest that the TAM likely evolved from an original combination of BamA and TamB, with a later gene duplication event of BamA, giving rise to an additional Omp85 sequence that evolved to be TamA in Proteobacteria and TamL in Bacteroidetes/Chlorobi.
MeSH term(s)	Amino Acid Motifs ; Bacterial Outer Membrane Proteins/chemistry ; Bacterial Outer Membrane Proteins/classification ; Bacterial Outer Membrane Proteins/genetics ; Bacteroidetes/genetics ; Evolution, Molecular ; Genetic Variation ; Multigene Family ; Phylogeny ; Proteobacteria/genetics
Chemical Substances	Bacterial Outer Membrane Proteins
Language	English
Publishing date	2015-05-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evv097
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Bacterial retrons encode phage-defending tripartite toxin-antitoxin systems.

Nature

2022 Volume 609, Issue 7925, Page(s) 144–150

Abstract: Retrons are prokaryotic genetic retroelements encoding a reverse transcriptase that produces multi-copy single-stranded ... ...

Abstract	Retrons are prokaryotic genetic retroelements encoding a reverse transcriptase that produces multi-copy single-stranded DNA
MeSH term(s)	Antitoxins/genetics ; Bacteriophages/metabolism ; DNA, Bacterial/genetics ; DNA, Single-Stranded/genetics ; Nucleic Acid Conformation ; Prophages/metabolism ; RNA-Directed DNA Polymerase/metabolism ; Retroelements/genetics ; Salmonella typhimurium/genetics ; Salmonella typhimurium/growth & development ; Salmonella typhimurium/virology ; Toxin-Antitoxin Systems/genetics
Chemical Substances	Antitoxins ; DNA, Bacterial ; DNA, Single-Stranded ; Retroelements ; RNA-Directed DNA Polymerase (EC 2.7.7.49)
Language	English
Publishing date	2022-07-18
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-05091-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito