LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 67

Search options

  1. Article ; Online: From structure to mechanism: skiing the energy landscape.

    Kern, Dorothee

    Nature methods

    2021  Volume 18, Issue 5, Page(s) 435–436

    MeSH term(s) Protein Conformation ; Proteins/chemistry ; Thermodynamics
    Chemical Substances Proteins
    Language English
    Publishing date 2021-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-021-01140-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6022: 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.

  2. Article ; Online: Response to Comment on "Ancient origins of allosteric activation in a Ser-Thr kinase".

    Wilson, Christopher / Kern, Dorothee

    Science (New York, N.Y.)

    2020  Volume 370, Issue 6519

    Abstract: ... ...

    Abstract Park
    MeSH term(s) Cell Cycle Proteins ; Microtubule-Associated Proteins ; Protein-Serine-Threonine Kinases/genetics
    Chemical Substances Cell Cycle Proteins ; Microtubule-Associated Proteins ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2020-11-19
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abd0364
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 27: 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 77: 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.

  3. Article ; Online: A biophysical framework for double-drugging kinases.

    Kim, Chansik / Ludewig, Hannes / Hadzipasic, Adelajda / Kutter, Steffen / Nguyen, Vy / Kern, Dorothee

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

    2023  Volume 120, Issue 34, Page(s) e2304611120

    Abstract: Selective orthosteric inhibition of kinases has been challenging due to the conserved active site architecture of kinases and emergence of resistance mutants. Simultaneous inhibition of distant orthosteric and allosteric sites, which we refer to as " ... ...

    Abstract Selective orthosteric inhibition of kinases has been challenging due to the conserved active site architecture of kinases and emergence of resistance mutants. Simultaneous inhibition of distant orthosteric and allosteric sites, which we refer to as "double-drugging", has recently been shown to be effective in overcoming drug resistance. However, detailed biophysical characterization of the cooperative nature between orthosteric and allosteric modulators has not been undertaken. Here, we provide a quantitative framework for double-drugging of kinases employing isothermal titration calorimetry, Förster resonance energy transfer, coupled-enzyme assays, and X-ray crystallography. We discern positive and negative cooperativity for Aurora A kinase (AurA) and Abelson kinase (Abl) with different combinations of orthosteric and allosteric modulators. We find that a conformational equilibrium shift is the main principle governing cooperativity. Notably, for both kinases, we find a synergistic decrease of the required orthosteric and allosteric drug dosages when used in combination to inhibit kinase activities to clinically relevant inhibition levels. X-ray crystal structures of the double-drugged kinase complexes reveal the molecular principles underlying the cooperative nature of double-drugging AurA and Abl with orthosteric and allosteric inhibitors. Finally, we observe a fully closed conformation of Abl when bound to a pair of positively cooperative orthosteric and allosteric modulators, shedding light on the puzzling abnormality of previously solved closed Abl structures. Collectively, our data provide mechanistic and structural insights into rational design and evaluation of double-drugging strategies.
    MeSH term(s) Humans ; Crystallography, X-Ray ; Imatinib Mesylate/chemistry ; Imatinib Mesylate/pharmacology ; Niacinamide/chemistry ; Niacinamide/pharmacology ; Proto-Oncogene Proteins c-abl/antagonists & inhibitors ; Proto-Oncogene Proteins c-abl/chemistry ; Aurora Kinase A/antagonists & inhibitors ; Aurora Kinase A/chemistry ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology
    Chemical Substances ABL1 protein, human (EC 2.7.10.2) ; AURKA protein, human (EC 2.7.11.1) ; asciminib ; Imatinib Mesylate (8A1O1M485B) ; Niacinamide (25X51I8RD4) ; Proto-Oncogene Proteins c-abl (EC 2.7.10.2) ; Aurora Kinase A (EC 2.7.11.1) ; Protein Kinase Inhibitors
    Language English
    Publishing date 2023-08-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.2304611120
    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.

  4. Article ; Online: Cumulative mechanism of several major imatinib-resistant mutations in Abl kinase.

    Hoemberger, Marc / Pitsawong, Warintra / Kern, Dorothee

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

    2020  Volume 117, Issue 32, Page(s) 19221–19227

    Abstract: Despite the outstanding success of the cancer drug imatinib, one obstacle in prolonged treatment is the emergence of resistance mutations within the kinase domain of its target, Abl. We noticed that many patient-resistance mutations occur in the dynamic ... ...

    Abstract Despite the outstanding success of the cancer drug imatinib, one obstacle in prolonged treatment is the emergence of resistance mutations within the kinase domain of its target, Abl. We noticed that many patient-resistance mutations occur in the dynamic hot spots recently identified to be responsible for imatinib's high selectivity toward Abl. In this study, we provide an experimental analysis of the mechanism underlying drug resistance for three major resistance mutations (G250E, Y253F, and F317L). Our data settle controversies, revealing unexpected resistance mechanisms. The mutations alter the energy landscape of Abl in complex ways: increased kinase activity, altered affinity, and cooperativity for the substrates, and, surprisingly, only a modestly decreased imatinib affinity. Only under cellular adenosine triphosphate (ATP) concentrations, these changes cumulate in an order of magnitude increase in imatinib's half-maximal inhibitory concentration (IC
    MeSH term(s) Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Antineoplastic Agents/pharmacology ; Drug Resistance, Neoplasm ; Humans ; Imatinib Mesylate/pharmacology ; Neoplasms/drug therapy ; Neoplasms/enzymology ; Neoplasms/genetics ; Oncogene Proteins v-abl/chemistry ; Oncogene Proteins v-abl/genetics ; Oncogene Proteins v-abl/metabolism
    Chemical Substances Antineoplastic Agents ; Oncogene Proteins v-abl ; Imatinib Mesylate (8A1O1M485B) ; Adenosine Triphosphate (8L70Q75FXE)
    Keywords covid19
    Language English
    Publishing date 2020-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1919221117
    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: Structure determination of high-energy states in a dynamic protein ensemble.

    Stiller, John B / Otten, Renee / Häussinger, Daniel / Rieder, Pascal S / Theobald, Douglas L / Kern, Dorothee

    Nature

    2022  Volume 603, Issue 7901, Page(s) 528–535

    Abstract: Macromolecular function frequently requires that proteins change conformation into high-energy ... ...

    Abstract Macromolecular function frequently requires that proteins change conformation into high-energy states
    MeSH term(s) Adenylate Kinase/metabolism ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Thermodynamics
    Chemical Substances Adenylate Kinase (EC 2.7.4.3)
    Language English
    Publishing date 2022-03-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-022-04468-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    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

    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.

  6. Article ; Online: From primordial clocks to circadian oscillators.

    Pitsawong, Warintra / Pádua, Ricardo A P / Grant, Timothy / Hoemberger, Marc / Otten, Renee / Bradshaw, Niels / Grigorieff, Nikolaus / Kern, Dorothee

    Nature

    2023  Volume 616, Issue 7955, Page(s) 183–189

    Abstract: Circadian rhythms play an essential part in many biological processes, and only three prokaryotic proteins are required to constitute a true post-translational circadian ... ...

    Abstract Circadian rhythms play an essential part in many biological processes, and only three prokaryotic proteins are required to constitute a true post-translational circadian oscillator
    MeSH term(s) Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Bacterial Proteins/ultrastructure ; Circadian Clocks ; Circadian Rhythm ; Phosphorylation ; Rhodobacter sphaeroides/chemistry ; Rhodobacter sphaeroides/metabolism ; Crystallography, X-Ray ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism ; Adenosine Diphosphate/metabolism ; Kinetics ; Protein Folding ; Protein Conformation ; Allosteric Regulation
    Chemical Substances Bacterial Proteins ; Adenosine Triphosphate (8L70Q75FXE) ; Adenosine Diphosphate (61D2G4IYVH)
    Language English
    Publishing date 2023-03-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-05836-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    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

    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.

  7. Article ; Online: Predicting multiple conformations via sequence clustering and AlphaFold2.

    Wayment-Steele, Hannah K / Ojoawo, Adedolapo / Otten, Renee / Apitz, Julia M / Pitsawong, Warintra / Hömberger, Marc / Ovchinnikov, Sergey / Colwell, Lucy / Kern, Dorothee

    Nature

    2023  Volume 625, Issue 7996, Page(s) 832–839

    Abstract: AlphaFold2 (ref. ...

    Abstract AlphaFold2 (ref.
    MeSH term(s) Cluster Analysis ; Mutation ; Protein Conformation ; Proteins/chemistry ; Proteins/genetics ; Proteins/metabolism ; Sequence Alignment ; Machine Learning ; Rhodobacter sphaeroides ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Protein Folding
    Chemical Substances Proteins ; Bacterial Proteins ; mpt53 protein, Mycobacterium tuberculosis
    Language English
    Publishing date 2023-11-13
    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/s41586-023-06832-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    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

    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.

  8. Article: Cumulative mechanism of several major imatinib-resistant mutations in Abl kinase

    Hoemberger, Marc / Pitsawong, Warintra / Kern, Dorothee

    Proc. Natl. Acad. Sci. U. S. A

    Abstract: Despite the outstanding success of the cancer drug imatinib, one obstacle in prolonged treatment is the emergence of resistance mutations within the kinase domain of its target, Abl. We noticed that many patient-resistance mutations occur in the dynamic ... ...

    Abstract Despite the outstanding success of the cancer drug imatinib, one obstacle in prolonged treatment is the emergence of resistance mutations within the kinase domain of its target, Abl. We noticed that many patient-resistance mutations occur in the dynamic hot spots recently identified to be responsible for imatinib's high selectivity toward Abl. In this study, we provide an experimental analysis of the mechanism underlying drug resistance for three major resistance mutations (G250E, Y253F, and F317L). Our data settle controversies, revealing unexpected resistance mechanisms. The mutations alter the energy landscape of Abl in complex ways: increased kinase activity, altered affinity, and cooperativity for the substrates, and, surprisingly, only a modestly decreased imatinib affinity. Only under cellular adenosine triphosphate (ATP) concentrations, these changes cumulate in an order of magnitude increase in imatinib's half-maximal inhibitory concentration (IC50). These results highlight the importance of characterizing energy landscapes of targets and its changes by drug binding and by resistance mutations developed by patients.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32719139
    Database COVID19

    Kategorien

    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.

  9. Book ; Thesis: Die Topographie der Eingeweide der Körperhöhle des Haushuhnes (Gallus domesticus)

    Kern, Dorothee

    unter besonderer Berücksichtigung der Serosa- und Gekröseverhältnisse

    1963  

    Institution Justus-Liebig-Universität Gießen
    Author's details eingereicht von Dorothee Kern
    Language German
    Size 71 Seiten
    Publishing place Gießen
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Justus Liebig-Universität zu Gießen, 1963
    HBZ-ID HT000656304
    Database Catalogue ZB MED Nutrition, Environment, Agriculture

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Shelf markLoan statusLocation
    DissJ 5418 order for loan Geschlossenes Magazin (U2)

    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.

  10. Article: Cutting the leash.

    Kern, Dorothee

    Nature structural biology

    2002  Volume 9, Issue 7, Page(s) 496–497

    MeSH term(s) Cyclophilin A/metabolism ; Gene Products, gag/chemistry ; Gene Products, gag/metabolism ; HIV Antigens/chemistry ; HIV Antigens/metabolism ; HIV-1/chemistry ; HIV-1/growth & development ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Nucleocapsid Proteins ; Peptide Fragments/chemistry ; Peptide Fragments/metabolism ; Protein Precursors/chemistry ; Protein Precursors/metabolism ; Protein Structure, Secondary ; Viral Proteins ; Virus Assembly ; gag Gene Products, Human Immunodeficiency Virus
    Chemical Substances Gene Products, gag ; HIV Antigens ; Nucleocapsid Proteins ; Peptide Fragments ; Protein Precursors ; Viral Proteins ; gag Gene Products, Human Immunodeficiency Virus ; p15 gag protein, Human immunodeficiency virus 1 ; p17 protein, Human Immunodeficiency Virus Type 1 ; p55 gag precursor protein, Human immunodeficiency virus 1 ; Cyclophilin A (EC 5.2.1.-)
    Language English
    Publishing date 2002-07
    Publishing country United States
    Document type Comment ; News
    ZDB-ID 1192623-5
    ISSN 1072-8368
    ISSN 1072-8368
    DOI 10.1038/nsb0702-496
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4101: 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.

To top