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  1. Article: Activity-based annotation: the emergence of systems biochemistry

    Rhee, Kyu Y. / Jansen, Robert S. / Grundner, Christoph

    Trends in biochemical sciences. 2022,

    2022  

    Abstract: Current tools to annotate protein function have failed to keep pace with the speed of DNA sequencing and exponentially growing number of proteins of unknown function (PUFs). A major contributing factor to this mismatch is the historical lack of high- ... ...

    Abstract Current tools to annotate protein function have failed to keep pace with the speed of DNA sequencing and exponentially growing number of proteins of unknown function (PUFs). A major contributing factor to this mismatch is the historical lack of high-throughput methods to experimentally determine biochemical activity. Activity-based methods, such as activity-based metabolite and protein profiling, are emerging as new approaches for unbiased, global, biochemical annotation of protein function. In this review, we highlight recent experimental, activity-based approaches that offer new opportunities to determine protein function in a biologically agnostic and systems-level manner.
    Keywords metabolites ; nucleotide sequences ; protein composition ; proteins ; sequence analysis
    Language English
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 194220-7
    ISSN 0968-0004 ; 0376-5067
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2022.03.017
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  2. Article ; Online: Mutations in

    Patel, Yesha / Soni, Vijay / Rhee, Kyu Y / Helmann, John D

    mBio

    2023  Volume 14, Issue 2, Page(s) e0316822

    Abstract: Bacteria can adapt to stressful conditions through mutations affecting the RNA polymerase core subunits that lead to beneficial changes in transcription. In response to selection with rifampicin (RIF), mutations arise in the RIF resistance-determining ... ...

    Abstract Bacteria can adapt to stressful conditions through mutations affecting the RNA polymerase core subunits that lead to beneficial changes in transcription. In response to selection with rifampicin (RIF), mutations arise in the RIF resistance-determining region (RRDR) of
    MeSH term(s) Rifampin/pharmacology ; Rifampin/therapeutic use ; Peptidoglycan/genetics ; beta-Lactams/pharmacology ; Cefuroxime/pharmacology ; Acetylglucosamine ; Mycobacterium tuberculosis/genetics ; Drug Resistance, Bacterial/genetics ; Mutation ; Uridine Diphosphate ; DNA-Directed RNA Polymerases/genetics ; Bacterial Proteins/genetics ; Bacterial Proteins/pharmacology ; Microbial Sensitivity Tests ; Antitubercular Agents/pharmacology
    Chemical Substances Rifampin (VJT6J7R4TR) ; Peptidoglycan ; beta-Lactams ; Cefuroxime (O1R9FJ93ED) ; Acetylglucosamine (V956696549) ; Uridine Diphosphate (58-98-0) ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; Bacterial Proteins ; Antitubercular Agents
    Language English
    Publishing date 2023-02-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.03168-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Activity-based annotation: the emergence of systems biochemistry.

    Rhee, Kyu Y / Jansen, Robert S / Grundner, Christoph

    Trends in biochemical sciences

    2022  Volume 47, Issue 9, Page(s) 785–794

    Abstract: Current tools to annotate protein function have failed to keep pace with the speed of DNA sequencing and exponentially growing number of proteins of unknown function (PUFs). A major contributing factor to this mismatch is the historical lack of high- ... ...

    Abstract Current tools to annotate protein function have failed to keep pace with the speed of DNA sequencing and exponentially growing number of proteins of unknown function (PUFs). A major contributing factor to this mismatch is the historical lack of high-throughput methods to experimentally determine biochemical activity. Activity-based methods, such as activity-based metabolite and protein profiling, are emerging as new approaches for unbiased, global, biochemical annotation of protein function. In this review, we highlight recent experimental, activity-based approaches that offer new opportunities to determine protein function in a biologically agnostic and systems-level manner.
    Language English
    Publishing date 2022-04-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2022.03.017
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    Zs.A 1207: Show issues Location:
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  4. Article: The

    Sachla, Ankita J / Soni, Vijay / Piñeros, Miguel / Luo, Yuanchan / Im, Janice J / Rhee, Kyu Y / Helmann, John D

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Microbes encounter a myriad of stresses during their life cycle. Dysregulation of metal ion homeostasis is increasingly recognized as a key factor in host-microbe interactions. Bacterial metal ion homeostasis is tightly regulated by dedicated ... ...

    Abstract Microbes encounter a myriad of stresses during their life cycle. Dysregulation of metal ion homeostasis is increasingly recognized as a key factor in host-microbe interactions. Bacterial metal ion homeostasis is tightly regulated by dedicated metalloregulators that control uptake, sequestration, trafficking, and efflux. Here, we demonstrate that deletion of the
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.14.580342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Genome-wide screen identifies host loci that modulate Mycobacterium tuberculosis fitness in immunodivergent mice.

    Meade, Rachel K / Long, Jarukit E / Jinich, Adrian / Rhee, Kyu Y / Ashbrook, David G / Williams, Robert W / Sassetti, Christopher M / Smith, Clare M

    G3 (Bethesda, Md.)

    2023  Volume 13, Issue 9

    Abstract: Genetic differences among mammalian hosts and among strains of Mycobacterium tuberculosis (Mtb) are well-established determinants of tuberculosis (TB) patient outcomes. The advent of recombinant inbred mouse panels and next-generation transposon ... ...

    Abstract Genetic differences among mammalian hosts and among strains of Mycobacterium tuberculosis (Mtb) are well-established determinants of tuberculosis (TB) patient outcomes. The advent of recombinant inbred mouse panels and next-generation transposon mutagenesis and sequencing approaches has enabled dissection of complex host-pathogen interactions. To identify host and pathogen genetic determinants of Mtb pathogenesis, we infected members of the highly diverse BXD family of strains with a comprehensive library of Mtb transposon mutants (TnSeq). Members of the BXD family segregate for Mtb-resistant C57BL/6J (B6 or B) and Mtb-susceptible DBA/2J (D2 or D) haplotypes. The survival of each bacterial mutant was quantified within each BXD host, and we identified those bacterial genes that were differentially required for Mtb fitness across BXD genotypes. Mutants that varied in survival among the host family of strains were leveraged as reporters of "endophenotypes," each bacterial fitness profile directly probing specific components of the infection microenvironment. We conducted quantitative trait loci (QTL) mapping of these bacterial fitness endophenotypes and identified 140 host-pathogen QTL (hpQTL). We located a QTL hotspot on chromosome 6 (75.97-88.58 Mb) associated with the genetic requirement of multiple Mtb genes: Rv0127 (mak), Rv0359 (rip2), Rv0955 (perM), and Rv3849 (espR). Together, this screen reinforces the utility of bacterial mutant libraries as precise reporters of the host immunological microenvironment during infection and highlights specific host-pathogen genetic interactions for further investigation. To enable downstream follow-up for both bacterial and mammalian genetic research communities, all bacterial fitness profiles have been deposited into GeneNetwork.org and added into the comprehensive collection of TnSeq libraries in MtbTnDB.
    MeSH term(s) Mice ; Animals ; Mycobacterium tuberculosis/genetics ; Mice, Inbred DBA ; Mice, Inbred C57BL ; Quantitative Trait Loci ; Mutagenesis ; Mammals/genetics
    Language English
    Publishing date 2023-06-29
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1093/g3journal/jkad147
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  6. Article: Genome-wide screen identifies host loci that modulate

    Meade, Rachel K / Long, Jarukit E / Jinich, Adrian / Rhee, Kyu Y / Ashbrook, David G / Williams, Robert W / Sassetti, Christopher M / Smith, Clare M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Genetic differences among mammalian hosts ... ...

    Abstract Genetic differences among mammalian hosts and
    Language English
    Publishing date 2023-03-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.05.528534
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Emerging Approaches to Tuberculosis Drug Development: At Home in the Metabolome.

    Jansen, Robert S / Rhee, Kyu Y

    Trends in pharmacological sciences

    2017  Volume 38, Issue 4, Page(s) 393–405

    Abstract: Once considered a crowning achievement of modern drug development, tuberculosis (TB) chemotherapy has proven increasingly unable to keep pace with the spread of the pandemic and rise of drug resistance. Efforts to revive the TB drug development pipeline ... ...

    Abstract Once considered a crowning achievement of modern drug development, tuberculosis (TB) chemotherapy has proven increasingly unable to keep pace with the spread of the pandemic and rise of drug resistance. Efforts to revive the TB drug development pipeline have, in the meantime, faltered. Closer analysis reveals key experimental deficiencies that have hindered our ability to 'reverse engineer' knowledge of antibiotic mechanisms into rational drug development. Here, we discuss the emerging potential of metabolomics; the systems level study of small molecule metabolites, to help overcome these gaps and serve as a unique biochemical bridge between the phenotypic properties of chemical compounds and biological targets.
    MeSH term(s) Antitubercular Agents/classification ; Antitubercular Agents/pharmacology ; Drug Discovery ; Drug Resistance, Microbial ; Humans ; Metabolomics
    Chemical Substances Antitubercular Agents
    Language English
    Publishing date 2017-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 282846-7
    ISSN 1873-3735 ; 0165-6147
    ISSN (online) 1873-3735
    ISSN 0165-6147
    DOI 10.1016/j.tips.2017.01.005
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    Zs.A 1513: Show issues Location:
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    Zs.MG 6: Show issues

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  8. Article: Identification of a proteolysis regulator for an essential enzyme in

    Kahne, Shoshanna C / Yoo, Jin Hee / Chen, James / Nakedi, Kehilwe / Iyer, Lakshminarayan M / Putzel, Gregory / Samhadaneh, Nora M / Pironti, Alejandro / Aravind, L / Ekiert, Damian C / Bhabha, Gira / Rhee, Kyu Y / Darwin, K Heran

    bioRxiv : the preprint server for biology

    2024  

    Abstract: In : One sentence summary: A pseudo-pantothenate kinase regulates proteasomal degradation of a pantothenate synthesis enzyme ... ...

    Abstract In
    One sentence summary: A pseudo-pantothenate kinase regulates proteasomal degradation of a pantothenate synthesis enzyme in
    Language English
    Publishing date 2024-03-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.29.587195
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Growth of

    Gouzy, Alexandre / Healy, Claire / Black, Katherine A / Rhee, Kyu Y / Ehrt, Sabine

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

    2021  Volume 118, Issue 32

    Abstract: Acidic pH arrests the growth ... ...

    Abstract Acidic pH arrests the growth of
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Carbon/metabolism ; Carbon Isotopes/analysis ; Carbon Isotopes/metabolism ; Gluconeogenesis ; Glucose/metabolism ; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism ; Glycerol/metabolism ; Host-Pathogen Interactions/physiology ; Hydrogen-Ion Concentration ; Isocitrate Lyase/metabolism ; Lipid Metabolism ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/growth & development ; Mycobacterium tuberculosis/metabolism ; Oleic Acid/metabolism ; Oleic Acid/pharmacology ; Phosphoenolpyruvate Carboxykinase (ATP)/metabolism ; Reactive Oxygen Species
    Chemical Substances Bacterial Proteins ; Carbon Isotopes ; Reactive Oxygen Species ; Oleic Acid (2UMI9U37CP) ; Carbon (7440-44-0) ; Glyceraldehyde-3-Phosphate Dehydrogenases (EC 1.2.1.-) ; Phosphoenolpyruvate Carboxykinase (ATP) (EC 4.1.1.49) ; Isocitrate Lyase (EC 4.1.3.1) ; Carbon-13 (FDJ0A8596D) ; Glucose (IY9XDZ35W2) ; Glycerol (PDC6A3C0OX)
    Language English
    Publishing date 2021-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2024571118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1148: Show issues Location:
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  10. Article ; Online: Metabolic principles of persistence and pathogenicity in Mycobacterium tuberculosis.

    Ehrt, Sabine / Schnappinger, Dirk / Rhee, Kyu Y

    Nature reviews. Microbiology

    2018  Volume 16, Issue 8, Page(s) 496–507

    Abstract: Metabolism was once relegated to the supply of energy and biosynthetic precursors, but it has now become clear that it is a specific mediator of nearly all physiological processes. In the context of microbial pathogenesis, metabolism has expanded outside ...

    Abstract Metabolism was once relegated to the supply of energy and biosynthetic precursors, but it has now become clear that it is a specific mediator of nearly all physiological processes. In the context of microbial pathogenesis, metabolism has expanded outside its canonical role in bacterial replication. Among human pathogens, this expansion has emerged perhaps nowhere more visibly than for Mycobacterium tuberculosis, the causative agent of tuberculosis. Unlike most pathogens, M. tuberculosis has evolved within humans, which are both host and reservoir. This makes unrestrained replication and perpetual quiescence equally incompatible strategies for survival as a species. In this Review, we summarize recent work that illustrates the diversity of metabolic functions that not only enable M. tuberculosis to establish and maintain a state of chronic infection within the host but also facilitate its survival in the face of drug pressure and, ultimately, completion of its life cycle.
    MeSH term(s) Energy Metabolism ; Host-Pathogen Interactions ; Humans ; Mycobacterium tuberculosis/metabolism ; Mycobacterium tuberculosis/pathogenicity ; Tuberculosis/microbiology ; Virulence
    Language English
    Publishing date 2018-04-24
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2139054-X
    ISSN 1740-1534 ; 1740-1526
    ISSN (online) 1740-1534
    ISSN 1740-1526
    DOI 10.1038/s41579-018-0013-4
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    Zs.A 5865: Show issues Location:
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