Robert Fick

Ph.D. Student

Areas of Interest

Methyltransferases make up approximately 1% of human gene products, and these enzymes most commonly use S-adenosyl-L-methionine (AdoMet) as the methyl-donating cofactor. Work by the Trievel labratory noted close interactions between the active site oxygen atoms in a SET domain lysine methyltransferase and the AdoMet methyl group, indicating non-canonical carbon-oxygen (CH•••O) hydrogen bonding. These CH•••O hydrogen bonds were shown in studies of the lysine methyltransferase SET7/9 to greatly affect AdoMet binding, and are also important in catalysis. A survey of high resolution AdoMet-bound methyltransferase structures within the Protein Data Bank found these interactions are conserved across six different classes of methyltransferase. I am continuing the characterization of the roles for CH•••O hydrogen bonding in the largest and most diverse class of methyltransferases, the Rossmann fold-like methyltransferases, using the model methyltransferase TylM1. Through the use of binding studies and enzyme kinetic assays I am characterizing the roles of hydrogen bonding to the AdoMet methyl and methylene groups neighboring the sulfonium cation. In addition, I am working towards determining the neutron and ultra-high resolution X-ray structures of TylM1 bound to AdoMet to define the methyl hydrogen atom positions, allowing the CH•••O hydrogen bond distances and angles to be experimentally measured within the active site.

Mentor:  Dr. Raymond Trievel

Published Articles or Reviews

Fick RJ, Kroner GM, Nepal B, Magnani R, Horowitz S, Houtz RL, Scheiner S, Trievel RC. Sulfer-Oxygen Chalcogen Bonding Mediates AdoMet Recognition in the Lysine Methyltransferase SET7/9.  ACS Chem Biol 2016 Jan 12 (Epub ahead of print)
Fick, RJ, Trievel RC.  An overview of chromatin modifications.  Biopolymers.  2013 Feb;99(2):95-7. doi: 10.1002/bip.22158.