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  1. Article ; Online: Role of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Inflammation and Pathogen-Associated Interactions.

    Truthe, Sarah / Klassert, Tilman E / Schmelz, Stefan / Jonigk, Danny / Blankenfeldt, Wulf / Slevogt, Hortense

    Journal of innate immunity

    2024  Volume 16, Issue 1, Page(s) 105–132

    Abstract: Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its ... ...

    Abstract Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its involvement in cancer, ischemic stroke, and diabetes. LOX-1 is a C-type lectin receptor and is involved in the activation of immune cells and inflammatory processes. It may further interact with pathogens, suggesting a role in infections or the host's response.
    Summary: This review compiles the current knowledge of potential implications of LOX-1 in inflammatory processes and in host-pathogen interactions with a particular emphasis on its regulatory role in immune responses. Also discussed are genomic and structural variations found in LOX-1 homologs across different species as well as potential involvements of LOX-1 in inflammatory processes from the angle of different cell types and organ-specific interactions.
    Key messages: The results presented reveal both similar and different structures in human and murine LOX-1 and provide clues as to the possible origins of different modes of interaction. These descriptions raise concerns about the suitability, particularly of mouse models, that are often used in the analysis of its functionality in humans. Further research should also aim to better understand the mostly unknown binding and interaction mechanisms between LOX-1 and different pathogens. This pursuit will not only enhance our understanding of LOX-1 involvement in inflammatory processes but also identify potential targets for immunomodulatory approaches.
    MeSH term(s) Animals ; Humans ; Mice ; Atherosclerosis/immunology ; Atherosclerosis/metabolism ; Host-Pathogen Interactions/immunology ; Inflammation/immunology ; Lipoproteins, LDL/metabolism ; Scavenger Receptors, Class E/metabolism ; Scavenger Receptors, Class E/genetics
    Chemical Substances Lipoproteins, LDL ; OLR1 protein, human ; oxidized low density lipoprotein ; Scavenger Receptors, Class E
    Language English
    Publishing date 2024-01-17
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454158-8
    ISSN 1662-8128 ; 1662-811X
    ISSN (online) 1662-8128
    ISSN 1662-811X
    DOI 10.1159/000535793
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Online ; Thesis: Untersuchungen zur Stabilisierung des Transkriptionsfaktors RhlR durch die Thioesterase PqsE in Pseudomonas aeruginosa

    Borgert, Sebastian Roman Verfasser] / [Blankenfeldt, Wulf [Akademischer Betreuer] / Jahn, Dieter [Akademischer Betreuer]

    2024  

    Author's details Sebastian Roman Borgert ; Wulf Blankenfeldt, Dieter Jahn
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language German
    Publisher Technische Universität Braunschweig
    Publishing place Braunschweig
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  3. Article ; Online: Structure of heme d

    Klünemann, Thomas / Blankenfeldt, Wulf

    Acta crystallographica. Section F, Structural biology communications

    2020  Volume 76, Issue Pt 6, Page(s) 250–256

    Abstract: A key step in anaerobic nitrate respiration is the reduction of nitrite to nitric oxide, which is catalysed by the ... ...

    Abstract A key step in anaerobic nitrate respiration is the reduction of nitrite to nitric oxide, which is catalysed by the cd
    MeSH term(s) Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Crystallography, X-Ray ; Heme/analogs & derivatives ; Heme/chemistry ; Heme/metabolism ; Models, Molecular ; Nitrite Reductases/chemistry ; Nitrite Reductases/metabolism ; Protein Conformation ; Pseudomonas aeruginosa/enzymology
    Chemical Substances Bacterial Proteins ; Heme (42VZT0U6YR) ; heme d1 (59948-35-5) ; Nitrite Reductases (EC 1.7.-)
    Language English
    Publishing date 2020-05-29
    Publishing country United States
    Document type Journal Article
    ISSN 2053-230X
    ISSN (online) 2053-230X
    DOI 10.1107/S2053230X20006676
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Amino acid positions near the active site determine the reduced activity of human ACOD1 compared to murine ACOD1.

    Chen, Fangfang / Yalcin, Israfil / Zhao, Mingming / Chen, Chutao / Blankenfeldt, Wulf / Pessler, Frank / Büssow, Konrad

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 10360

    Abstract: cis-Aconitate decarboxylase (ACOD1, IRG1) converts cis-aconitate to the immunomodulatory and antibacterial metabolite itaconate. Although the active site residues of human and mouse ACOD1 are identical, the mouse enzyme is about fivefold more active. ... ...

    Abstract cis-Aconitate decarboxylase (ACOD1, IRG1) converts cis-aconitate to the immunomodulatory and antibacterial metabolite itaconate. Although the active site residues of human and mouse ACOD1 are identical, the mouse enzyme is about fivefold more active. Aiming to identify the cause of this difference, we mutated positions near the active site in human ACOD1 to the corresponding residues of mouse ACOD1 and measured resulting activities in vitro and in transfected cells. Interestingly, Homo sapiens is the only species with methionine instead of isoleucine at residue 154 and introduction of isoleucine at this position increased the activity of human ACOD1 1.5-fold in transfected cells and 3.5-fold in vitro. Enzyme activity of gorilla ACOD1, which is almost identical to the human enzyme but has isoleucine at residue 154, was similar to the mouse enzyme in vitro. Met154 in human ACOD1 forms a sulfur-π bond to Phe381, which is positioned to impede access of the substrate to the active site. It appears that the ACOD1 sequence has changed at position 154 during human evolution, resulting in a pronounced decrease in activity. This change might have offered a selective advantage in diseases such as cancer.
    MeSH term(s) Animals ; Humans ; Mice ; Amino Acids ; Catalytic Domain ; Isoleucine ; Carboxy-Lyases/chemistry
    Chemical Substances Amino Acids ; Isoleucine (04Y7590D77) ; ACOD1 protein, human (EC 4.1.1.-) ; Carboxy-Lyases (EC 4.1.1.-) ; Irg1 protein, mouse (EC 4.2.1.79)
    Language English
    Publishing date 2023-06-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-37373-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: High-resolution structure of eukaryotic Fibrillarin interacting with Nop56 amino-terminal domain.

    Höfler, Simone / Lukat, Peer / Blankenfeldt, Wulf / Carlomagno, Teresa

    RNA (New York, N.Y.)

    2021  Volume 27, Issue 4, Page(s) 496–512

    Abstract: Ribosomal RNA (rRNA) carries extensive 2'-O-methyl marks at functionally important sites. This simple chemical modification is thought to confer stability, promote RNA folding, and contribute to generate a heterogenous ribosome population with a yet- ... ...

    Abstract Ribosomal RNA (rRNA) carries extensive 2'-O-methyl marks at functionally important sites. This simple chemical modification is thought to confer stability, promote RNA folding, and contribute to generate a heterogenous ribosome population with a yet-uncharacterized function. 2'-O-methylation occurs both in archaea and eukaryotes and is accomplished by the Box C/D RNP enzyme in an RNA-guided manner. Extensive and partially conflicting structural information exists for the archaeal enzyme, while no structural data is available for the eukaryotic enzyme. The yeast Box C/D RNP consists of a guide RNA, the RNA-primary binding protein Snu13, the two scaffold proteins Nop56 and Nop58, and the enzymatic module Nop1. Here we present the high-resolution structure of the eukaryotic Box C/D methyltransferase Nop1 from
    MeSH term(s) Amino Acid Sequence ; Archaeal Proteins/chemistry ; Archaeal Proteins/genetics ; Archaeal Proteins/metabolism ; Binding Sites ; Chromosomal Proteins, Non-Histone/chemistry ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Crystallography, X-Ray ; Gene Expression ; Methylation ; Models, Molecular ; Nuclear Proteins/chemistry ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Interaction Domains and Motifs ; Pyrococcus furiosus/genetics ; Pyrococcus furiosus/metabolism ; RNA, Fungal/genetics ; RNA, Fungal/metabolism ; RNA, Ribosomal/genetics ; RNA, Ribosomal/metabolism ; RNA, Small Nucleolar/genetics ; RNA, Small Nucleolar/metabolism ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Ribonucleoproteins, Small Nuclear/chemistry ; Ribonucleoproteins, Small Nuclear/genetics ; Ribonucleoproteins, Small Nuclear/metabolism ; Ribonucleoproteins, Small Nucleolar/chemistry ; Ribonucleoproteins, Small Nucleolar/genetics ; Ribonucleoproteins, Small Nucleolar/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/chemistry ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Sequence Alignment ; Structural Homology, Protein ; RNA, Guide, CRISPR-Cas Systems
    Chemical Substances Archaeal Proteins ; Chromosomal Proteins, Non-Histone ; NOP1 protein, S cerevisiae ; NOP56 protein, S cerevisiae ; NOP58 protein, S cerevisiae ; Nuclear Proteins ; RNA, Fungal ; RNA, Ribosomal ; RNA, Small Nucleolar ; Recombinant Proteins ; Ribonucleoproteins, Small Nuclear ; Ribonucleoproteins, Small Nucleolar ; Saccharomyces cerevisiae Proteins ; Snu13 protein, S cerevisiae ; fibrillarin
    Language English
    Publishing date 2021-01-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1241540-6
    ISSN 1469-9001 ; 1355-8382
    ISSN (online) 1469-9001
    ISSN 1355-8382
    DOI 10.1261/rna.077396.120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Eukaryotic Box C/D methylation machinery has two non-symmetric protein assembly sites.

    Höfler, Simone / Lukat, Peer / Blankenfeldt, Wulf / Carlomagno, Teresa

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 17561

    Abstract: Box C/D ribonucleoprotein complexes are RNA-guided methyltransferases that methylate the ribose 2'-OH of RNA. The central 'guide RNA' has box C and D motifs at its ends, which are crucial for activity. Archaeal guide RNAs have a second box C'/D' motif ... ...

    Abstract Box C/D ribonucleoprotein complexes are RNA-guided methyltransferases that methylate the ribose 2'-OH of RNA. The central 'guide RNA' has box C and D motifs at its ends, which are crucial for activity. Archaeal guide RNAs have a second box C'/D' motif pair that is also essential for function. This second motif is poorly conserved in eukaryotes and its function is uncertain. Conflicting literature data report that eukaryotic box C'/D' motifs do or do not bind proteins specialized to recognize box C/D-motifs and are or are not important for function. Despite this uncertainty, the architecture of eukaryotic 2'-O-methylation enzymes is thought to be similar to that of their archaeal counterpart. Here, we use biochemistry, X-ray crystallography and mutant analysis to demonstrate the absence of functional box C'/D' motifs in more than 80% of yeast guide RNAs. We conclude that eukaryotic Box C/D RNPs have two non-symmetric protein assembly sites and that their three-dimensional architecture differs from that of archaeal 2'-O-methylation enzymes.
    MeSH term(s) Archaea/genetics ; Eukaryota/genetics ; Methylation ; Methyltransferases/metabolism ; RNA/genetics ; RNA, Small Nucleolar/metabolism ; Ribonucleoproteins/metabolism ; RNA, Guide, CRISPR-Cas Systems
    Chemical Substances RNA, Small Nucleolar ; Ribonucleoproteins ; RNA (63231-63-0) ; Methyltransferases (EC 2.1.1.-)
    Language English
    Publishing date 2021-09-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-97030-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Molecular replacement for small-molecule crystal structure determination from X-ray and electron diffraction data with reduced resolution.

    Gorelik, Tatiana E / Lukat, Peer / Kleeberg, Christian / Blankenfeldt, Wulf / Mueller, Rolf

    Acta crystallographica. Section A, Foundations and advances

    2023  Volume 79, Issue Pt 6, Page(s) 504–514

    Abstract: The resolution of 3D electron diffraction (ED) data of small-molecule crystals is often relatively poor, due to either electron-beam radiation damage during data collection or poor crystallinity of the material. Direct methods, used as standard for ... ...

    Abstract The resolution of 3D electron diffraction (ED) data of small-molecule crystals is often relatively poor, due to either electron-beam radiation damage during data collection or poor crystallinity of the material. Direct methods, used as standard for crystal structure determination, are not applicable when the data resolution falls below the commonly accepted limit of 1.2 Å. Therefore an evaluation was carried out of the performance of molecular replacement (MR) procedures, regularly used for protein structure determination, for structure analysis of small-molecule crystal structures from 3D ED data. In the course of this study, two crystal structures of Bi-3812, a highly potent inhibitor of the oncogenic transcription factor BCL6, were determined: the structure of α-Bi-3812 was determined from single-crystal X-ray data, the structure of β-Bi-3812 from 3D ED data, using direct methods in both cases. These data were subsequently used for MR with different data types, varying the data resolution limit (1, 1.5 and 2 Å) and by using search models consisting of connected or disconnected fragments of BI-3812. MR was successful with 3D ED data at 2 Å resolution using a search model that represented 74% of the complete molecule.
    Language English
    Publishing date 2023-10-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2020844-3
    ISSN 2053-2733 ; 1600-5724 ; 0108-7673
    ISSN (online) 2053-2733 ; 1600-5724
    ISSN 0108-7673
    DOI 10.1107/S2053273323008458
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Structure-function relationships underpin disulfide loop cleavage-dependent activation of Legionella pneumophila lysophospholipase A PlaA.

    Hiller, Miriam / Diwo, Maurice / Wamp, Sabrina / Gutsmann, Thomas / Lang, Christina / Blankenfeldt, Wulf / Flieger, Antje

    Molecular microbiology

    2023  Volume 121, Issue 3, Page(s) 497–512

    Abstract: Legionella pneumophila, the causative agent of a life-threatening pneumonia, intracellularly replicates in a specialized compartment in lung macrophages, the Legionella-containing vacuole (LCV). Secreted proteins of the pathogen govern important steps in ...

    Abstract Legionella pneumophila, the causative agent of a life-threatening pneumonia, intracellularly replicates in a specialized compartment in lung macrophages, the Legionella-containing vacuole (LCV). Secreted proteins of the pathogen govern important steps in the intracellular life cycle including bacterial egress. Among these is the type II secreted PlaA which, together with PlaC and PlaD, belongs to the GDSL phospholipase family found in L. pneumophila. PlaA shows lysophospholipase A (LPLA) activity which increases after secretion and subsequent processing by the zinc metalloproteinase ProA within a disulfide loop. Activity of PlaA contributes to the destabilization of the LCV in the absence of the type IVB-secreted effector SdhA. We here present the 3D structure of PlaA which shows a typical α/β-hydrolase fold and reveals that the uncleaved disulfide loop forms a lid structure covering the catalytic triad S30/D278/H282. This leads to reduction of substrate access before activation; however, the catalytic site gets more accessible when the disulfide loop is processed. After structural modeling, a similar activation process is suggested for the GDSL hydrolase PlaC, but not for PlaD. Furthermore, the size of the PlaA substrate-binding site indicated preference toward phospholipids comprising ~16 carbon fatty acid residues which was verified by lipid hydrolysis, suggesting a molecular ruler mechanism. Indeed, mutational analysis changed the substrate profile with respect to fatty acid chain length. In conclusion, our analysis revealed the structural basis for the regulated activation and substrate preference of PlaA.
    MeSH term(s) Lysophospholipase/genetics ; Lysophospholipase/metabolism ; Legionella pneumophila/genetics ; Legionella pneumophila/metabolism ; Bacterial Proteins/metabolism ; Disulfides/metabolism ; Vacuoles/metabolism ; Fatty Acids/metabolism ; Structure-Activity Relationship
    Chemical Substances Lysophospholipase (EC 3.1.1.5) ; Bacterial Proteins ; Disulfides ; Fatty Acids
    Language English
    Publishing date 2023-12-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.15201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Book ; Online ; Thesis: Design and characterization of stable variants of the quorum sensing regulator RhlR from Pseudomonas aeruginosa

    Henke, Steffi [Verfasser] / Blankenfeldt, Wulf [Akademischer Betreuer] / Jahn, Dieter [Akademischer Betreuer]

    2023  

    Author's details Steffi Henke ; Wulf Blankenfeldt, Dieter Jahn
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Technische Universität Braunschweig
    Publishing place Braunschweig
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  10. Article ; Online: Structure of heme d-free cd nitrite reductase NirS.

    Klünemann, Thomas / Blankenfeldt, Wulf

    76 ; Pt 6 ; 250 ; 256 ; Acta crystallographica. Section F, Structural biology communications ; United States

    2020  

    Abstract: A key step in anaerobic nitrate respiration is the reduction of nitrite to nitric oxide, which is catalysed by the cd1 nitrite reductase NirS in, for example, the Gram-negative opportunistic pathogen Pseudomonas aeruginosa. Each subunit of this ... ...

    Abstract A key step in anaerobic nitrate respiration is the reduction of nitrite to nitric oxide, which is catalysed by the cd1 nitrite reductase NirS in, for example, the Gram-negative opportunistic pathogen Pseudomonas aeruginosa. Each subunit of this homodimeric enzyme consists of a cytochrome c domain and an eight-bladed β-propeller that binds the uncommon isobacteriochlorin heme d1 as an essential part of its active site. Although NirS has been well studied mechanistically and structurally, the focus of previous studies has been on the active heme d1-bound form. The heme d1-free form of NirS reported here, which represents a premature state of the reductase, adopts an open conformation with the cytochrome c domains moved away from each other with respect to the active enzyme. Further, the movement of a loop around Trp498 seems to be related to a widening of the propeller, allowing easier access to the heme d1-binding side. Finally, a possible link between the open conformation of NirS and flagella formation in P. aeruginosa is discussed.
    Keywords NirS ; cd1 nitrite reductase ; heme d1
    Subject code 540
    Language English
    Publishing date 2020-05-29
    Publisher International Union of Crystallography
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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