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  1. Article ; Online: Temporal and spatial resolution of distal protein motions that activate hydrogen tunneling in soybean lipoxygenase.

    Zaragoza, Jan Paulo T / Offenbacher, Adam R / Hu, Shenshen / Gee, Christine L / Firestein, Zachary M / Minnetian, Natalie / Deng, Zhenyu / Fan, Flora / Iavarone, Anthony T / Klinman, Judith P

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

    2023  Volume 120, Issue 10, Page(s) e2211630120

    Abstract: The enzyme soybean lipoxygenase (SLO) provides a prototype for deep tunneling mechanisms in hydrogen transfer catalysis. This work combines room temperature X-ray studies with extended hydrogen-deuterium exchange experiments to define a catalytically- ... ...

    Abstract The enzyme soybean lipoxygenase (SLO) provides a prototype for deep tunneling mechanisms in hydrogen transfer catalysis. This work combines room temperature X-ray studies with extended hydrogen-deuterium exchange experiments to define a catalytically-linked, radiating cone of aliphatic side chains that connects an active site iron center of SLO to the protein-solvent interface. Employing eight variants of SLO that have been appended with a fluorescent probe at the identified surface loop, nanosecond fluorescence Stokes shifts have been measured. We report a remarkable identity of the energies of activation (
    MeSH term(s) Lipoxygenase ; Glycine max ; Fluorescent Dyes ; Motion ; Hydrogen
    Chemical Substances Lipoxygenase (EC 1.13.11.12) ; Fluorescent Dyes ; Hydrogen (7YNJ3PO35Z)
    Language English
    Publishing date 2023-03-03
    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.2211630120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Hydrogen-deuterium exchange reveals long-range dynamical allostery in soybean lipoxygenase.

    Offenbacher, Adam R / Iavarone, Anthony T / Klinman, Judith P

    The Journal of biological chemistry

    2017  Volume 293, Issue 4, Page(s) 1138–1148

    Abstract: ... lipoxygenases also contain a 100-150-amino acid N-terminal C2-like domain that has been implicated ... conformational changes are detected both at the N-terminal domain and within the substrate portal nearly 30 Å ...

    Abstract In lipoxygenases, the topologically conserved C-terminal domain catalyzes the oxidation of polyunsaturated fatty acids, generating an assortment of biologically relevant signaling mediators. Plant and animal lipoxygenases also contain a 100-150-amino acid N-terminal C2-like domain that has been implicated in interactions with isolated fatty acids and at the phospholipid bilayer. These interactions may lead to increased substrate availability and contribute to the regulation of active-site catalysis. Because of a lack of structural information, a molecular understanding of this lipid-protein interaction remains unresolved. Herein, we employed hydrogen-deuterium exchange MS (HDXMS) to spatially resolve changes in protein conformation upon interaction of soybean lipoxygenase with a fatty acid surrogate, oleyl sulfate (OS), previously shown to act at a site separate from the substrate-binding site. Specific, OS-induced conformational changes are detected both at the N-terminal domain and within the substrate portal nearly 30 Å away. Combining previously measured kinetic properties in the presence of OS with its impact on the
    MeSH term(s) Allosteric Regulation ; Deuterium Exchange Measurement ; Linoleic Acid/chemistry ; Lipoxygenase/chemistry ; Protein Domains ; Soybean Proteins/chemistry ; Glycine max/enzymology ; Substrate Specificity
    Chemical Substances Soybean Proteins ; Linoleic Acid (9KJL21T0QJ) ; Lipoxygenase (EC 1.13.11.12)
    Language English
    Publishing date 2017-11-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M117.817197
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  3. Article: Repertoire diversification of primary vs memory B cell subsets.

    Klinman, N R

    Current topics in microbiology and immunology

    1998  Volume 229, Page(s) 133–148

    MeSH term(s) Animals ; Antibody Diversity/immunology ; B-Lymphocyte Subsets/immunology ; Immunologic Memory
    Language English
    Publishing date 1998-01-01
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 0070-217X
    ISSN 0070-217X
    DOI 10.1007/978-3-642-71984-4_10
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  4. Article ; Online: Detecting and Characterizing the Kinetic Activation of Thermal Networks in Proteins: Thermal Transfer from a Distal, Solvent-Exposed Loop to the Active Site in Soybean Lipoxygenase.

    Zaragoza, Jan Paulo T / Nguy, Andy / Minnetian, Natalie / Deng, Zhenyu / Iavarone, Anthony T / Offenbacher, Adam R / Klinman, Judith P

    The journal of physical chemistry. B

    2019  Volume 123, Issue 41, Page(s) 8662–8674

    Abstract: The rate-limiting chemical reaction catalyzed by soybean lipoxygenase (SLO) involves quantum mechanical tunneling of a hydrogen atom from substrate to its active site ferric-hydroxide cofactor. SLO has emerged as a prototypical system for linking the ... ...

    Abstract The rate-limiting chemical reaction catalyzed by soybean lipoxygenase (SLO) involves quantum mechanical tunneling of a hydrogen atom from substrate to its active site ferric-hydroxide cofactor. SLO has emerged as a prototypical system for linking the thermal activation of a protein scaffold to the efficiency of active site chemistry. Significantly, hydrogen-deuterium exchange-mass spectrometry (HDX-MS) experiments on wild type and mutant forms of SLO have uncovered trends in the enthalpic barriers for HDX within a solvent-exposed loop (positions 317-334) that correlate well with trends in the corresponding enthalpic barriers for
    MeSH term(s) Binding Sites ; Catalysis ; Catalytic Domain ; Kinetics ; Lipoxygenase/chemistry ; Lipoxygenase/metabolism ; Models, Molecular ; Protein Conformation ; Solvents/chemistry ; Glycine max/enzymology ; Temperature ; Thermodynamics
    Chemical Substances Solvents ; Lipoxygenase (EC 1.13.11.12)
    Language English
    Publishing date 2019-10-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1520-5207
    ISSN (online) 1520-5207
    DOI 10.1021/acs.jpcb.9b07228
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The cellular origins of memory B cells.

    Klinman, N R

    Seminars in immunology

    1997  Volume 9, Issue 4, Page(s) 241–247

    Abstract: Recent evidence indicates that memory B cells may originate from a precursor cell subset that is distinct from AFC precursors. Most convincing is the finding that fractionation of naive peripheral B-cell populations on the basis of surface heat stable ... ...

    Abstract Recent evidence indicates that memory B cells may originate from a precursor cell subset that is distinct from AFC precursors. Most convincing is the finding that fractionation of naive peripheral B-cell populations on the basis of surface heat stable antigen (HSA) expression yields two populations; one greatly enriched for progenitors of memory B cells (HSAlo), and the other enriched for AFC precursors (HSAint-hi). Antigenic stimulation of HSAlo B cells in vitro leads to the generation of memory B-cell clones in the absence of any detectable antibody formation whereas stimulation of HSAint-hi cells yield AFC responses but not memory B cells. Furthermore, the progeny of HSAlo cells are unique in their ability to accumulate somatic mutations and originate germinal centers (GC). The pre-existence of two distinct precursor cell populations may help resolve the disparate biological characteristics of AFC precursors which appear to be terminally differentiated versus memory progenitors which retain stem cell characteristics in their capacity to self renew, undergo multiple divisions, and generate progeny that express enzymes characteristic of stem cells or pro-pre B cells and acquire tolerance susceptibility.
    MeSH term(s) Animals ; Antibody-Producing Cells/cytology ; Antibody-Producing Cells/immunology ; B-Lymphocyte Subsets/cytology ; B-Lymphocyte Subsets/immunology ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; Cell Differentiation ; Germinal Center/cytology ; Germinal Center/immunology ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/immunology ; Humans ; Immunologic Memory ; Models, Biological
    Language English
    Publishing date 1997-08
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1006/smim.1997.0075
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    Zs.A 2843: Show issues Location:
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  6. Article: The "clonal selection hypothesis" and current concepts of B cell tolerance.

    Klinman, N R

    Immunity

    1996  Volume 5, Issue 3, Page(s) 189–195

    MeSH term(s) Animals ; Antigens, Surface/immunology ; B-Lymphocytes/immunology ; Humans ; Immune Tolerance ; Immunologic Memory
    Chemical Substances Antigens, Surface
    Language English
    Publishing date 1996-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/s1074-7613(00)80314-3
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    Zs.MG 69: Show issues

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  7. Article: In vitro analysis of the generation and propagation of memory B cells.

    Klinman, N R

    Immunological reviews

    1996  Volume 150, Page(s) 91–111

    MeSH term(s) Animals ; B-Lymphocyte Subsets/immunology ; B-Lymphocytes/immunology ; Cell Division ; Cells, Cultured ; Flow Cytometry/methods ; Germinal Center/immunology ; Hybridomas/immunology ; Immune Tolerance ; Immunologic Memory ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, SCID ; Models, Immunological ; Mutation/immunology
    Language English
    Publishing date 1996-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/j.1600-065x.1996.tb00697.x
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  8. Article ; Online: Plasmacytoid dendritic cell response to CpG ODN correlates with CXCL16 expression and is inhibited by ox-LDL.

    Gursel, Mayda / Klinman, Dennis M / Gursel, Ihsan

    Mediators of inflammation

    2013  Volume 2013, Page(s) 312590

    Abstract: Structurally distinct classes of synthetic CpG oligonucleotides (ODN) differentially activate human immune cells. K-type ODN trigger plasmacytoid dendritic cells (pDCs) to differentiate and produce TNF α . In contrast, D-type ODN stimulate large amounts ... ...

    Abstract Structurally distinct classes of synthetic CpG oligonucleotides (ODN) differentially activate human immune cells. K-type ODN trigger plasmacytoid dendritic cells (pDCs) to differentiate and produce TNF α . In contrast, D-type ODN stimulate large amounts of IFN α secretion from pDCs. The cell-surface receptor CXCL16 was previously shown to influence the nature and specificity of CpG ODN-induced immune activation. Here, we evaluated the expression and function of CXCL16 on pDC from healthy volunteers. We report that increased CXCL16 expression correlated with enhanced in vitro response exclusively to D-type CpG ODN. Conversely, enzymatic digestion of the receptor resulted in a decrease in IFN α production. Moreover, ox-LDL presence significantly inhibited D-ODN mediated IFN α production by pDCs. Coculture of enriched pDCs with the CXCR6 expressing Jurkat T cells decreased the activation threshold of these cells responding to D-ODN, suggesting that CXCL16/CXCR6 interaction may play an important role in modifying the response of pDCs to environmental danger signals.
    MeSH term(s) Chemokine CXCL16 ; Chemokines, CXC/metabolism ; Coculture Techniques ; Cytokines/metabolism ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Dipeptides/chemistry ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gene Expression Regulation ; Healthy Volunteers ; Humans ; Interferon-alpha/metabolism ; Jurkat Cells ; Leukocytes, Mononuclear/cytology ; Lipoproteins, LDL/metabolism ; Oligodeoxyribonucleotides/chemistry ; Receptors, CXCR6 ; Receptors, Chemokine/metabolism ; Receptors, Scavenger/metabolism ; Receptors, Virus/metabolism ; Signal Transduction
    Chemical Substances CPG-oligonucleotide ; CXCL16 protein, human ; CXCR6 protein, human ; Chemokine CXCL16 ; Chemokines, CXC ; Cytokines ; Dipeptides ; Interferon-alpha ; Lipoproteins, LDL ; N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide ; Oligodeoxyribonucleotides ; Receptors, CXCR6 ; Receptors, Chemokine ; Receptors, Scavenger ; Receptors, Virus ; oxidized low density lipoprotein
    Language English
    Publishing date 2013-11-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1137605-3
    ISSN 1466-1861 ; 0962-9351
    ISSN (online) 1466-1861
    ISSN 0962-9351
    DOI 10.1155/2013/312590
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  9. Article: Selection in the expression of functionally distinct B-cell subsets.

    Klinman, N R

    Current opinion in immunology

    1994  Volume 6, Issue 3, Page(s) 420–424

    Abstract: Although the isolation and characterization of functionally distinct B-cell subsets has been a major preoccupation of immunologists for the past two decades, only recently has it been recognized that the various B-cell subsets may be disparately selected ...

    Abstract Although the isolation and characterization of functionally distinct B-cell subsets has been a major preoccupation of immunologists for the past two decades, only recently has it been recognized that the various B-cell subsets may be disparately selected during their development and maturation on the basis of their expressed Ig V regions. Thus, pre-B cells are selected for clonal expansion and maturation by virtue of the amino-acid sequence of their nascent H chains and newly emerging B cells may be selected for longevity and subset distribution on the basis of both clonotype-specific and relatively non-specific interactions of their surface Ig receptors.
    MeSH term(s) Animals ; B-Lymphocyte Subsets/cytology ; Cell Differentiation ; Humans
    Language English
    Publishing date 1994-06
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/0952-7915(94)90121-x
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    Zs.MG 13: Show issues

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  10. Article: Cellular response to partial hepatectomy.

    KLINMAN, N R / ERSLEV, A J

    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)

    2003  Volume 112, Page(s) 338–340

    MeSH term(s) Cell Division ; Cell Nucleus ; Hepatectomy ; Liver
    Language English
    Publishing date 2003-09-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 4015-0
    ISSN 1535-3699 ; 1525-1373 ; 0037-9727
    ISSN (online) 1535-3699 ; 1525-1373
    ISSN 0037-9727
    DOI 10.3181/00379727-112-28037
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