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  1. Article ; Online: Decipher enzymes from human microbiota for drug discovery and development.

    Beliaeva, Mariia A / Wilmanns, Matthias / Zimmermann, Michael

    Current opinion in structural biology

    2023  Volume 80, Page(s) 102567

    Abstract: The human microbiota plays an important role in human health and contributes to the metabolism of therapeutic drugs affecting their potency. However, the current knowledge on human gut bacterial metabolism is limited and lacks an understanding of the ... ...

    Abstract The human microbiota plays an important role in human health and contributes to the metabolism of therapeutic drugs affecting their potency. However, the current knowledge on human gut bacterial metabolism is limited and lacks an understanding of the underlying mechanisms of observed drug biotransformations. Despite the complexity of the gut microbial community, genomic and metagenomic sequencing provides insights into the diversity of chemical reactions that can be carried out by the microbiota and poses new challenges to functionally annotate thousands of bacterial enzymes. Here, we outline methods to systematically address the structural and functional space of the human microbiome, highlighting a combination of in silico and in vitro approaches. Systematic knowledge about microbial enzymes could eventually be applied for personalized therapy, the development of prodrugs and modulators of unwanted bacterial activity, and the further discovery of new antibiotics.
    MeSH term(s) Humans ; Gastrointestinal Microbiome ; Microbiota ; Bacteria/genetics ; Genomics ; Drug Discovery
    Language English
    Publishing date 2023-03-22
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1068353-7
    ISSN 1879-033X ; 0959-440X
    ISSN (online) 1879-033X
    ISSN 0959-440X
    DOI 10.1016/j.sbi.2023.102567
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Versatile allosteric properties in Pex5-like tetratricopeptide repeat proteins to induce diverse downstream function.

    Bürgi, Jérôme / Ekal, Lakhan / Wilmanns, Matthias

    Traffic (Copenhagen, Denmark)

    2021  Volume 22, Issue 5, Page(s) 140–152

    Abstract: Proteins composed of tetratricopeptide repeat (TPR) arrays belong to the α-solenoid tandem-repeat family that have unique properties in terms of their overall conformational flexibility and ability to bind to multiple protein ligands. The peroxisomal ... ...

    Abstract Proteins composed of tetratricopeptide repeat (TPR) arrays belong to the α-solenoid tandem-repeat family that have unique properties in terms of their overall conformational flexibility and ability to bind to multiple protein ligands. The peroxisomal matrix protein import receptor Pex5 comprises two TPR triplets that recognize protein cargos with a specific C-terminal Peroxisomal Targeting Signal (PTS) 1 motif. Import of PTS1-containing protein cargos into peroxisomes through a transient pore is mainly driven by allosteric binding, coupling and release mechanisms, without a need for external energy. A very similar TPR architecture is found in the functionally unrelated TRIP8b, a regulator of the hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel. TRIP8b binds to the HCN ion channel via a C-terminal sequence motif that is nearly identical to the PTS1 motif of Pex5 receptor cargos. Pex5, Pex5-related Pex9, and TRIP8b also share a less conserved N-terminal domain. This domain provides a second protein cargo-binding site and plays a distinct role in allosteric coupling of initial cargo loading by PTS1 motif-mediated interactions and different downstream functional readouts. The data reviewed here highlight the overarching role of molecular allostery in driving the diverse functions of TPR array proteins, which could form a model for other α-solenoid tandem-repeat proteins involved in translocation processes across membranes.
    MeSH term(s) Carrier Proteins/metabolism ; Peroxisome-Targeting Signal 1 Receptor/metabolism ; Peroxisomes/metabolism ; Protein Binding ; Protein Transport ; Tetratricopeptide Repeat
    Chemical Substances Carrier Proteins ; Peroxisome-Targeting Signal 1 Receptor
    Language English
    Publishing date 2021-02-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1483852-7
    ISSN 1600-0854 ; 1398-9219
    ISSN (online) 1600-0854
    ISSN 1398-9219
    DOI 10.1111/tra.12785
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Online ; Thesis: Structural and functional insights into a mycobacterial type VII secretion system

    Ritter, Christina [Verfasser] / Wilmanns, Matthias [Akademischer Betreuer]

    2022  

    Author's details Christina Ritter ; Betreuer: Matthias Wilmanns
    Keywords Naturwissenschaften ; Science
    Subject code sg500
    Language English
    Publisher Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky
    Publishing place Hamburg
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  4. Article ; Online: Across scales: novel insights into kidney health and disease by structural biology.

    Tomas, Nicola M / Mortensen, Simon A / Wilmanns, Matthias / Huber, Tobias B

    Kidney international

    2021  Volume 100, Issue 2, Page(s) 281–288

    Abstract: Over the past decades, structural biology methods such as X-ray crystallography and cryo-electron microscopy have been increasingly used to study protein functions, molecular interactions, physiological processes, and disease mechanisms. This review ... ...

    Abstract Over the past decades, structural biology methods such as X-ray crystallography and cryo-electron microscopy have been increasingly used to study protein functions, molecular interactions, physiological processes, and disease mechanisms. This review outlines a selection of structural biology methods, highlights recent examples of how structural analyses have contributed to a more profound understanding of the machinery of life, and gives a perspective on how these methods can be applied to investigate functions of kidney molecules and pathogenic mechanisms of renal diseases.
    MeSH term(s) Biology ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Kidney ; Proteins
    Chemical Substances Proteins
    Language English
    Publishing date 2021-04-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2021.03.042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Asymmetric horseshoe-like assembly of peroxisomal yeast oxalyl-CoA synthetase.

    Bürgi, Jérôme / Lill, Pascal / Giannopoulou, Evdokia-Anastasia / Jeffries, Cy M / Chojnowski, Grzegorz / Raunser, Stefan / Gatsogiannis, Christos / Wilmanns, Matthias

    Biological chemistry

    2023  Volume 404, Issue 2-3, Page(s) 195–207

    Abstract: Oxalyl-CoA synthetase ... ...

    Abstract Oxalyl-CoA synthetase from
    MeSH term(s) Saccharomyces cerevisiae/metabolism ; Amino Acid Sequence ; Cryoelectron Microscopy ; Microbodies/chemistry ; Microbodies/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Ligases/analysis ; Ligases/metabolism
    Chemical Substances oxalyl-coenzyme A ; Saccharomyces cerevisiae Proteins ; Ligases (EC 6.-)
    Language English
    Publishing date 2023-01-26
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1334659-3
    ISSN 1437-4315 ; 1431-6730 ; 1432-0355
    ISSN (online) 1437-4315
    ISSN 1431-6730 ; 1432-0355
    DOI 10.1515/hsz-2022-0273
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Online: Strukturelle und funktionelle Unterschiede in therapeutisch-relevanten "Targets" der M. tuberculosis (Beijing) und M. africanum Familie

    Wilmanns, Matthias

    Schlussbericht ; Berichtszeitraum: 01. Juli 2006 bis 30. Juni 2009

    2009  

    Title variant Structural/functional differences in selected targets from members of the M. tuberculosis (Beijing) and M. africanum families
    Author's details Autor des Berichts: Wilmanns, Matthias
    Language German
    Size Online-Ressource (13 S., 712 KB), Ill., graph. Darst.
    Publisher Technische Informationsbibliothek u. Universitätsbibliothek ; EMBL
    Publishing place Hannover ; Heidelberg
    Document type Book ; Online
    Note Förderkennzeichen BMBF 0313801L. - Verbund-Nr. 01048446. - Engl. Berichtsbl. u.d.T.: Structural/functional differences in selected targets from members of the M. tuberculosis (Beijing) and M. africanum families ; Unterschiede zwischen der elektronischen Ressource und dem gedruckten Dokument können nicht ausgeschlossen werden. - Auch als gedr. Ausg. vorhanden
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  7. Article ; Online: The ATPases of the mycobacterial type VII secretion system: Structural and mechanistic insights into secretion.

    Crosskey, Thomas D / Beckham, Katherine S H / Wilmanns, Matthias

    Progress in biophysics and molecular biology

    2019  Volume 152, Page(s) 25–34

    Abstract: Tuberculosis (TB) remains the foremost cause of death by infectious disease and is propagated by the pathogen Mycobacterium tuberculosis (Mtb). The virulence associated with Mtb is mediated by proteins secreted into host cells by the type VII secretion ... ...

    Abstract Tuberculosis (TB) remains the foremost cause of death by infectious disease and is propagated by the pathogen Mycobacterium tuberculosis (Mtb). The virulence associated with Mtb is mediated by proteins secreted into host cells by the type VII secretion system (T7SS), making this system a candidate for future drug and vaccine development. However, while many of the components involved in the T7SS have been identified, the mechanism of translocation across both the inner and outer mycobacterial membranes remains largely unexplained. Key to the translocation of proteins across the membrane is the activity of conserved AAA+ ATPases EccA and EccC, which are explored in this review. Although the T7SS does not appear homologous to other known bacterial secretion systems, many of those require ATPase activity during different phases of protein translocation. Thus, exploring the roles of ATPases in multiple secretion systems may provide insights into the T7SS. Targeting bacterial virulence factors such as secretion systems is becoming an increasingly explored area of research, and here we review how such strategies could be applied to the T7SS.
    MeSH term(s) Adenosine Triphosphatases/metabolism ; Bacterial Proteins/metabolism ; Cell Membrane/metabolism ; Models, Molecular ; Mycobacterium tuberculosis/metabolism ; Mycobacterium tuberculosis/ultrastructure ; Protein Binding ; Protein Conformation ; Signal Transduction ; Type VII Secretion Systems/metabolism ; Virulence
    Chemical Substances Bacterial Proteins ; Type VII Secretion Systems ; Adenosine Triphosphatases (EC 3.6.1.-)
    Language English
    Publishing date 2019-11-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 209302-9
    ISSN 1873-1732 ; 0079-6107
    ISSN (online) 1873-1732
    ISSN 0079-6107
    DOI 10.1016/j.pbiomolbio.2019.11.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The pMy vector series: A versatile cloning platform for the recombinant production of mycobacterial proteins in Mycobacterium smegmatis.

    Beckham, Katherine S H / Staack, Sonja / Wilmanns, Matthias / Parret, Annabel H A

    Protein science : a publication of the Protein Society

    2020  Volume 29, Issue 12, Page(s) 2528–2537

    Abstract: Structural and biophysical characterization of molecular mechanisms of disease-causing pathogens, such as Mycobacterium tuberculosis, often requires recombinant expression of large amounts highly pure protein. For the production of mycobacterial proteins, ...

    Abstract Structural and biophysical characterization of molecular mechanisms of disease-causing pathogens, such as Mycobacterium tuberculosis, often requires recombinant expression of large amounts highly pure protein. For the production of mycobacterial proteins, overexpression in the fast-growing and non-pathogenic species Mycobacterium smegmatis has several benefits over the standard Escherichia coli expression strains. However, unlike for E. coli, the range of expression vectors currently available is limited. Here we describe the development of the pMy vector series, a set of expression plasmids for recombinant production of single proteins and protein complexes in M. smegmatis. By incorporating an alternative selection marker, we show that these plasmids can also be used for co-expression studies. All vectors in the pMy vector series are available in the Addgene repository (www.addgene.com).
    MeSH term(s) Cloning, Molecular ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Genetic Vectors ; Mycobacterium smegmatis/genetics ; Mycobacterium smegmatis/metabolism ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/metabolism ; Plasmids/genetics ; Plasmids/metabolism ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics
    Chemical Substances Recombinant Proteins
    Language English
    Publishing date 2020-10-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1106283-6
    ISSN 1469-896X ; 0961-8368
    ISSN (online) 1469-896X
    ISSN 0961-8368
    DOI 10.1002/pro.3962
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Book ; Online: Schlußbericht "X-MTB Strukturgenomik - Konsortium Hamburg", Teilprojekt: Strukturproteomik durch Röntgenstrukturanalyse

    Wilmanns, Matthias

    Vorhabenbezeichnung: Hochdurchsatzkristallisation und Röntgenstrukturanalyse ; Laufzeit des Vorhabens/Berichtszeitraum: 1/5/2003 - 31/10/2006

    2007  

    Title variant X-MTB Strukturgenomik - Konsortium Hamburg, Teilprojekt: Strukturproteomik durch Röntgenstrukturanalyse
    Institution European Molecular Biology Laboratory
    Author's details Zuwendungsempfänger: Europäisches Molekularbiologie Laboratorium. Matthias Wilmanns (verantwortlich)
    Language German ; English
    Size Online-Ressource (26 S., 489 KB), Ill., graph. Darst.
    Publisher Technische Informationsbibliothek u. Universitätsbibliothek
    Publishing place Hannover ; Hamburg
    Document type Book ; Online
    Note Text teilw. dt., teilw. engl. ; Förderkennzeichen BMBF 0312992A ; Unterschiede zwischen der elektronischen Ressource und dem gedruckten Dokument können nicht ausgeschlossen werden
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  10. Book: Schlußbericht "X-MTB Strukturgenomik - Konsortium Hamburg", Teilprojekt: Strukturproteomik durch Röntgenstrukturanalyse

    Wilmanns, Matthias

    Vorhabenbezeichnung: Hochdurchsatzkristallisation und Röntgenstrukturanalyse ; Laufzeit des Vorhabens/Berichtszeitraum: 1/5/2003 - 31/10/2006

    2007  

    Title variant X-MTB Strukturgenomik - Konsortium Hamburg, Teilprojekt: Strukturproteomik durch Röntgenstrukturanalyse
    Institution European Molecular Biology Laboratory
    Author's details Zuwendungsempfänger: Europäisches Molekularbiologie Laboratorium. Matthias Wilmanns (verantwortlich)
    Language German ; English
    Size 29, [1] Bl., Ill., graph. Darst.
    Publishing place Hamburg
    Document type Book
    Note Text teilw. dt., teilw. engl. ; Förderkennzeichen BMBF 0312992A. - Verbund-Nr. 01023665 ; Unterschiede zwischen dem gedruckten Dokument und der elektronischen Ressource können nicht ausgeschlossen werden
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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