Raymond C Trievel
Professor
Department of Biological Chemistry
1150 West Medical Center Drive
Ann Arbor, MI 48109
[email protected]

Available to mentor

Raymond C Trievel
Professor
  • About
  • Links
  • Qualifications
  • Center Memberships
  • Research Overview
  • Recent Publications
  • About

    Our laboratory uses a combination of structural and biochemical approaches to study the structures, mechanisms, and substrate specificities of a variety of enzymes, with a particular focus on histone modifying enzymes.

    Links
    • Trievel Laboratory
    Qualifications
    • NIH IRTA Postdoctoral Fellow
      National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2003
    • PhD
      University of Pennsylvania, Philadelphia, 2000
    • BS
      University of Delaware, Newark, 1995
    Center Memberships
    • Center Member
      Caswell Diabetes Institute
    Research Overview

    1. Structural and Functional Studies of Histone Modifications: Histone modifying enzymes establish and maintain chromatin modifications states that play fundamental roles in governing transcription, DNA damage response, epigenetic gene regulation, and other genomic processes. Our laboratory has characterized the molecular determinants of the substrate specificities of several human histone modifying enzymes, including histone lysine methyltransferases and demethylases, employing structural and biochemical approaches. More recently, we have initiated a new research program aimed at understanding the functions of histone modifying enzymes expressed by bacterial pathogens. Theses enzymes are secreted by the pathogens into host cells where they enter the nucleus and hijack host gene expression by altering histone modifications, thus promoting bacterial replication. Structural and functional characterization of these enzymes from various bacterial pathogens, including Legionella pneumophila, the primary causative agent of Legionnaires’ Disease, is yielding novel insights the molecular basis of their unique histone substrate specificities. Together, these studies are illuminating new aspects of host-pathogen interactions and represent an emerging area of research at the interface of chromatin biology and microbiology.

    2. Mechanisms of AdoMet-dependent Methyltransferases: S-adenosylmethionine (AdoMet)-dependent methyltransferases methylate a diverse array of biological substrates, including proteins, nucleic acids, carbohydrates, lipids, cofactors, and hormones. Structural surveys of methyltransferases bound to AdoMet have revealed that the AdoMet methyl sulfonium cation engages in several types of unconventional non-bonded interactions, including methyl carbon-oxygen (CH---O) hydrogen bonding, sulfur chalcogen bonding, and methyl carbon tetrel bonding. The discovery of these unconventional bonds between the AdoMet methyl sulfonium cation and residues and ligands in methyltransferase active sites implicates these interactions in AdoMet binding and the SN2 reaction catalyzed by these enzymes. Using a model lysine methyltransferase and non-reactive lysine analogs, we are investigating the functional importance of these interactions in substrate recognition and catalysis using an interdisciplinary approach combining biochemistry, structural biology, spectroscopy, and computational chemistry. Collectively, these studies are elucidating the mechanisms by which CH---O hydrogen bonding, chalcogen bonding, and tetrel bonding promote AdoMet binding and catalysis in methyltransferases.

    Recent Publications See All Publications
    • Journal Article
      An optimized purification protocol for enzymatically synthesized S-adenosyl-L-methionine (SAM) for applications in solution state infrared spectroscopic studies.
      Odeyemi I, Douglas TA, Igie NF, Hargrove JA, Hamilton G, Bradley BB, Thai C, Le B, Unjia M, Wicherts D, Ferneyhough Z, Pillai A, Koirala S, Hagge LM, Polara H, Trievel RC, Fick RJ, Stelling AL. Spectrochim Acta A Mol Biomol Spectrosc, 2024 Mar 15; 309: 123816 DOI:10.1016/j.saa.2023.123816
      PMID: 38198991
    • Journal Article
      Intrinsic catalytic properties of histone H3 lysine-9 methyltransferases preserve monomethylation levels under low S-adenosylmethionine.
      Haws SA, Miller LJ, La Luz DR, Kuznetsov VI, Trievel RC, Craciun G, Denu JM. J Biol Chem, 2023 Jul; 299 (7): 104938 DOI:10.1016/j.jbc.2023.104938
      PMID: 37331600
    • Journal Article
      EZH2 T367 phosphorylation activates p38 signaling through lysine methylation to promote breast cancer progression.
      Gonzalez ME, Naimo GD, Anwar T, Paolì A, Tekula SR, Kim S, Medhora N, Leflein SA, Itkin J, Trievel R, Kidwell KM, Chen Y-C, Mauro L, Yoon E, Andò S, Kleer CG. iScience, 2022 Aug 19; 25 (8): 104827 DOI:10.1016/j.isci.2022.104827
      PMID: 35992062
    • Journal Article
      Molecular investigation of the tandem Tudor domain and plant homeodomain histone binding domains of the epigenetic regulator UHRF2.
      Ginnard SM, Winkler AE, Mellado Fritz C, Bluhm T, Kemmer R, Gilliam M, Butkevich N, Abdrabbo S, Bricker K, Feiler J, Miller I, Zoerman J, El-Mohri Z, Khuansanguan P, Basch M, Petzold T, Kostoff M, Konopka S, Kociba B, Gillis T, Heyl DL, Trievel RC, Albaugh BN. Proteins, 2022 Mar; 90 (3): 835 - 847. DOI:10.1002/prot.26278
      PMID: 34766381
    • Journal Article
      Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide adenine dinucleotide cofactors.
      Abshire ET, Hughes KL, Diao R, Pearce S, Gopalakrishna S, Trievel RC, Rorbach J, Freddolino PL, Goldstrohm AC. J Biol Chem, 2020 Oct 30; 295 (44): 15112 - 15133. DOI:10.1074/jbc.RA120.012618
      PMID: 32839274
    • Journal Article
      An H3K9 methylation-dependent protein interaction regulates the non-enzymatic functions of a putative histone demethylase.
      Raiymbek G, An S, Khurana N, Gopinath S, Larkin A, Biswas S, Trievel RC, Cho U-S, Ragunathan K. Elife, 2020 Mar 20; 9: DOI:10.7554/eLife.53155
      PMID: 32195666
    • Journal Article
      Structural and Functional Characterization of Sulfonium Carbon-Oxygen Hydrogen Bonding in the Deoxyamino Sugar Methyltransferase TylM1.
      Fick RJ, Horowitz S, McDole BG, Clay MC, Mehl RA, Al-Hashimi HM, Scheiner S, Trievel RC. Biochemistry, 2019 Apr 23; 58 (16): 2152 - 2159. DOI:10.1021/acs.biochem.8b01141
      PMID: 30810306
    • Journal Article
      Crystallographic and Computational Characterization of Methyl Tetrel Bonding in S-Adenosylmethionine-Dependent Methyltransferases.
      Trievel RC, Scheiner S. Molecules, 2018 Nov 13; 23 (11): DOI:10.3390/molecules23112965
      PMID: 30428636
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