LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article ; Online: Bicyclic Engineered Sortase A Performs Transpeptidation under Denaturing Conditions.

    Kiehstaller, Sebastian / Hutchins, George H / Amore, Alessia / Gerber, Alan / Ibrahim, Mohamed / Hennig, Sven / Neubacher, Saskia / Grossmann, Tom N

    Bioconjugate chemistry

    2023  Volume 34, Issue 6, Page(s) 1114–1121

    Abstract: Enzymes are of central importance to many biotechnological and biomedical applications. However, for many potential applications, the required conditions impede enzyme folding and therefore function. The enzyme Sortase A is a transpeptidase that is ... ...

    Abstract Enzymes are of central importance to many biotechnological and biomedical applications. However, for many potential applications, the required conditions impede enzyme folding and therefore function. The enzyme Sortase A is a transpeptidase that is widely used to perform bioconjugation reactions with peptides and proteins. Thermal and chemical stress impairs Sortase A activity and prevents its application under harsh conditions, thereby limiting the scope for bioconjugation reactions. Here, we report the stabilization of a previously reported, activity-enhanced Sortase A, which suffered from particularly low thermal stability, using the
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Aminoacyltransferases/metabolism ; Peptides ; Cysteine Endopeptidases/metabolism
    Chemical Substances sortase A (EC 2.3.2.-) ; Bacterial Proteins ; Aminoacyltransferases (EC 2.3.2.-) ; Peptides ; Cysteine Endopeptidases (EC 3.4.22.-)
    Language English
    Publishing date 2023-05-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1024041-x
    ISSN 1520-4812 ; 1043-1802
    ISSN (online) 1520-4812
    ISSN 1043-1802
    DOI 10.1021/acs.bioconjchem.3c00151
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3400: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    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.

  2. Article: Covalent bicyclization of protein complexes yields durable quaternary structures.

    Hutchins, George H / Kiehstaller, Sebastian / Poc, Pascal / Lewis, Abigail H / Oh, Jisun / Sadighi, Raya / Pearce, Nicholas M / Ibrahim, Mohamed / Drienovská, Ivana / Rijs, Anouk M / Neubacher, Saskia / Hennig, Sven / Grossmann, Tom N

    Chem

    2024  Volume 10, Issue 2, Page(s) 615–627

    Abstract: Proteins are essential biomolecules and central to biotechnological applications. In many cases, assembly into higher-order structures is a prerequisite for protein function. Under conditions relevant for applications, protein integrity is often ... ...

    Abstract Proteins are essential biomolecules and central to biotechnological applications. In many cases, assembly into higher-order structures is a prerequisite for protein function. Under conditions relevant for applications, protein integrity is often challenged, resulting in disassembly, aggregation, and loss of function. The stabilization of quaternary structure has proven challenging, particularly for trimeric and higher-order complexes, given the complexity of involved inter- and intramolecular interaction networks. Here, we describe the chemical bicyclization of homotrimeric protein complexes, thereby increasing protein resistance toward thermal and chemical stress. This approach involves the structure-based selection of cross-linking sites, their variation to cysteine, and a subsequent reaction with a triselectrophilic agent to form a protein assembly with bicyclic topology. Besides overall increased stability, we observe resistance toward aggregation and greatly prolonged shelf life. This bicyclization strategy gives rise to unprecedented protein chain topologies and can enable new biotechnological and biomedical applications.
    Language English
    Publishing date 2024-02-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2869032-1
    ISSN 2451-9294 ; 2451-9294 ; 2451-9308
    ISSN (online) 2451-9294
    ISSN 2451-9294 ; 2451-9308
    DOI 10.1016/j.chempr.2023.10.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    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.

  3. Article: Covalent Proteomimetic Inhibitor of the Bacterial FtsQB Divisome Complex

    Paulussen, Felix M. / Schouten, Gina K. / Moertl, Carolin / Verheul, Jolanda / Hoekstra, Irma / Koningstein, Gregory M. / Hutchins, George H. / Alkir, Aslihan / Luirink, Rosa A. / Geerke, Daan P. / van Ulsen, Peter / den Blaauwen, Tanneke / Luirink, Joen / Grossmann, Tom N.

    Journal of the American Chemical Society. 2022 Aug. 09, v. 144, no. 33

    2022  

    Abstract: The use of antibiotics is threatened by the emergence and spread of multidrug-resistant strains of bacteria. Thus, there is a need to develop antibiotics that address new targets. In this respect, the bacterial divisome, a multi-protein complex central ... ...

    Abstract The use of antibiotics is threatened by the emergence and spread of multidrug-resistant strains of bacteria. Thus, there is a need to develop antibiotics that address new targets. In this respect, the bacterial divisome, a multi-protein complex central to cell division, represents a potentially attractive target. Of particular interest is the FtsQB subcomplex that plays a decisive role in divisome assembly and peptidoglycan biogenesis in E. coli. Here, we report the structure-based design of a macrocyclic covalent inhibitor derived from a periplasmic region of FtsB that mediates its binding to FtsQ. The bioactive conformation of this motif was stabilized by a customized cross-link resulting in a tertiary structure mimetic with increased affinity for FtsQ. To increase activity, a covalent handle was incorporated, providing an inhibitor that impedes the interaction between FtsQ and FtsB irreversibly. The covalent inhibitor reduced the growth of an outer membrane-permeable E. coli strain, concurrent with the expected loss of FtsB localization, and also affected the infection of zebrafish larvae by a clinical E. coli strain. This first-in-class inhibitor of a divisome protein–protein interaction highlights the potential of proteomimetic molecules as inhibitors of challenging targets. In particular, the covalent mode-of-action can serve as an inspiration for future antibiotics that target protein–protein interactions.
    Keywords Danio rerio ; Escherichia coli ; biogenesis ; cell division ; multiple drug resistance ; peptidoglycans ; protein-protein interactions
    Language English
    Dates of publication 2022-0809
    Size p. 15303-15313.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.2c06304
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 55/32: Show issues
    Z 7.3: Show issues

    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.

    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.

  4. Article ; Online: An expandable, modular de novo protein platform for precision redox engineering.

    Hutchins, George H / Noble, Claire E M / Bunzel, H Adrian / Williams, Christopher / Dubiel, Paulina / Yadav, Sathish K N / Molinaro, Paul M / Barringer, Rob / Blackburn, Hector / Hardy, Benjamin J / Parnell, Alice E / Landau, Charles / Race, Paul R / Oliver, Thomas A A / Koder, Ronald L / Crump, Matthew P / Schaffitzel, Christiane / Oliveira, A Sofia F / Mulholland, Adrian J /
    Anderson, J L Ross

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 31, Page(s) e2306046120

    Abstract: The electron-conducting circuitry of life represents an as-yet untapped resource of exquisite, nanoscale biomolecular engineering. Here, we report the characterization and structure of a de novo diheme "maquette" protein, 4D2, which we subsequently use ... ...

    Abstract The electron-conducting circuitry of life represents an as-yet untapped resource of exquisite, nanoscale biomolecular engineering. Here, we report the characterization and structure of a de novo diheme "maquette" protein, 4D2, which we subsequently use to create an expanded, modular platform for heme protein design. A well-folded monoheme variant was created by computational redesign, which was then utilized for the experimental validation of continuum electrostatic redox potential calculations. This demonstrates how fundamental biophysical properties can be predicted and fine-tuned. 4D2 was then extended into a tetraheme helical bundle, representing a 7 nm molecular wire. Despite a molecular weight of only 24 kDa, electron cryomicroscopy illustrated a remarkable level of detail, indicating the positioning of the secondary structure and the heme cofactors. This robust, expressible, highly thermostable and readily designable modular platform presents a valuable resource for redox protein design and the future construction of artificial electron-conducting circuitry.
    MeSH term(s) Hemeproteins ; Biophysics ; Cryoelectron Microscopy ; Electrons ; Oxidation-Reduction
    Chemical Substances Hemeproteins
    Language English
    Publishing date 2023-07-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2306046120
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: 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)

    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.

  5. Article ; Online: Covalent Proteomimetic Inhibitor of the Bacterial FtsQB Divisome Complex.

    Paulussen, Felix M / Schouten, Gina K / Moertl, Carolin / Verheul, Jolanda / Hoekstra, Irma / Koningstein, Gregory M / Hutchins, George H / Alkir, Aslihan / Luirink, Rosa A / Geerke, Daan P / van Ulsen, Peter / den Blaauwen, Tanneke / Luirink, Joen / Grossmann, Tom N

    Journal of the American Chemical Society

    2022  Volume 144, Issue 33, Page(s) 15303–15313

    Abstract: The use of antibiotics is threatened by the emergence and spread of multidrug-resistant strains of bacteria. Thus, there is a need to develop antibiotics that address new targets. In this respect, the bacterial divisome, a multi-protein complex central ... ...

    Abstract The use of antibiotics is threatened by the emergence and spread of multidrug-resistant strains of bacteria. Thus, there is a need to develop antibiotics that address new targets. In this respect, the bacterial divisome, a multi-protein complex central to cell division, represents a potentially attractive target. Of particular interest is the FtsQB subcomplex that plays a decisive role in divisome assembly and peptidoglycan biogenesis in
    MeSH term(s) Animals ; Anti-Bacterial Agents/metabolism ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/metabolism ; Cell Cycle Proteins/chemistry ; Escherichia coli/metabolism ; Escherichia coli Proteins/chemistry ; Membrane Proteins/chemistry ; Zebrafish/metabolism
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Cell Cycle Proteins ; Escherichia coli Proteins ; Membrane Proteins
    Language English
    Publishing date 2022-08-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.2c06304
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 55/32: Show issues
    Z 7.3: Show issues

    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.

    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.

  6. Article ; Online: Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps.

    Chen, Jiun-Bo / James, Louisa K / Davies, Anna M / Wu, Yu-Chang Bryan / Rimmer, Joanne / Lund, Valerie J / Chen, Jou-Han / McDonnell, James M / Chan, Yih-Chih / Hutchins, George H / Chang, Tse Wen / Sutton, Brian J / Kariyawasam, Harsha H / Gould, Hannah J

    The Journal of allergy and clinical immunology

    2016  Volume 139, Issue 4, Page(s) 1195–1204.e11

    Abstract: Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form ... ...

    Abstract Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs.
    Objectives: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions.
    Methods: Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with "matched" heavy and light chains were cloned as IgG
    Results: Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG
    Conclusions: SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG
    MeSH term(s) Asthma, Aspirin-Induced/immunology ; Basophil Degranulation Test ; Basophils/immunology ; Cell Separation ; Chronic Disease ; Complementarity Determining Regions ; Enterotoxins/immunology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Immunoglobulin E/immunology ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Nasal Polyps/immunology ; Rhinitis/immunology ; Sinusitis/immunology ; Staphylococcus aureus/immunology ; Superantigens/immunology ; Surface Plasmon Resonance
    Chemical Substances Complementarity Determining Regions ; Enterotoxins ; Immunoglobulin G ; Superantigens ; enterotoxin E, Staphylococcal ; enterotoxin D, Staphylococcal (12788-99-7) ; enterotoxin A, Staphylococcal (37337-57-8) ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2016-09-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2016.06.066
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.92: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    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.

To top