Resume

• 2008

  Postdoctoral Fellow

  Published 12 papers

  including first authored manuscripts in Nature Chemical Biology

  Proceedings of the National Academy of Science

  and Journal of Molecular Biology; and a book chapter in Advances in Protein Chemistry and Structural Biology.\n\nProject leader in studies of protein-protein interactions in the context of heart abnormalities. \n\nGuided graduate and undergraduate researchers in peptide synthesis

  protein expression and purification

  and biophysical characterization of proteins. \n\nArtwork featured on the cover of Journal of Molecular Biology. \n\nFull support by a fellowship from the National Institutes of Health-Ruth Kirschstein award and the Minnesota Craniofacial Research Training (MinnCResT) Program. \n\nAwards including a Young Innovator award from CEM Corporation and the UofM BMBB department's Excellence in Postdoctoral Research. \n\nInvited speaker at the UofM Department of BMBB Seminar and Minneapolis Rotary Club. Guest lecturer for a course in Structural Biology.

  Biochemistry

  Molecular Biology

  and Biophysics

  University of Minnesota-Twin Cities

• 2004

  Ph.D.

  Dissertation titled “Towards the Full Molecular Details of Protein Kinase A Mediated Catalysis by NMR Spectrscopy”

  2009. \n\n10 publications including first authored manuscripts in Proceedings of the National Academy of Science USA

  Journal of the American Chemical Society

  and Biopolymers.\n\n\npre-Doctoral Fellowship awarded from the American Heart Assocation and additional support awarded through the National Institutes of Health-Chemical Biology Training Grant.\n\nOutstanding Teacher's Assistant Award in 2005.\n\nPlatform speaker at the 2008 52nd Annual Biophysical Society Meeting.\n\nTeacher's Assistant in: General Chemistry

  Organic Chemistry

  and the Nuclear Magnetic Resonance Structural Biology factility.

  Chemistry

  University of Minnesota-Twin Cities

• 1998

  Bachelors of Science

  ACS Certified

  Chemistry

  University of Wisconsin-La Crosse

• UV/Vis

  Organic Synthesis

  Research

  Chromatography

  Catalysis

  LC-MS

  Mass Spectrometry

  Structural Dynamics

  NMR spectroscopy

  HPLC

  Protein Kinases

  NMR

  Nuclear Magnetic Resonance (NMR)

  Chemistry

  Biochemistry

  Biophysics

  University Teaching

  Analytical Chemistry

  NMR Spectroscopy

  Organic Chemistry

  A Myristoyl/Phosphoserine Switch Controls cAMP-Dependent Protein Kinase Association to Membranes

  A Myristoyl/Phosphoserine Switch Controls cAMP-Dependent Protein Kinase Association to Membranes

  Gianluigi Veglia

  Jiali Gao

  Susan S. Taylor

  Christopher Mcclendon

  The catalytic subunit of protein kinase A (PKA-C) is subject to several post- or cotranslational modifications that regulate its activity both spatially and temporally. Among those

  N-myristoylation increases the kinase affinity for membranes and might also be implicated in substrate recognition and allosteric regulation. Here

  we investigated the effects of N-myristoylation on the structure

  dynamics

  and conformational equilibrium of PKA-C using atomistic molecular dynamics simulations. We found that the myristoyl group inserts into the hydrophobic pocket and leads to a tighter packing of the A-helix against the core of the enzyme. As a result

  the conformational dynamics of the A-helix are reduced and its motions are more coupled with the active site. Our simulations suggest that cation−π interactions among W30

  R190

  and R93 are responsible for coupling these motions. Two major conformations of the myristoylated N-terminus are the most populated: a long loop (LL conformation)

  similar to Protein Data Bank (PDB) entry 1CMK

  and a helix−turn−helix structure (HTH conformation)

  similar to PDB entry 4DFX

  which shows stronger coupling between the conformational dynamics observed at the A-helix and active site. The HTH conformation is stabilized by S10 phosphorylation of the kinase via ionic interactions between the protonated amine of K7 and the phosphate group on S10

  further enhancing the dynamic coupling to the active site. These results support a role of N-myristoylation in the allosteric regulation of PKA-C.

  Conformational Equilibrium of N‑Myristoylated cAMP-Dependent Protein Kinase A by Molecular Dynamics Simulations

  Expression and Purification of Isotopically Labeled Peptide Inhibitors and Substrates of cAMP-dependent Protein Kinase A for NMR Analysis

  The catalytic subunit of protein kinase A (PKA-C) is subject to several post- or cotranslational modifications that regulate its activity both spatially and temporally. Among those

  N-myristoylation increases the kinase affinity for membranes and might also be implicated in substrate recognition and allosteric regulation. Here

  we investigated the effects of N-myristoylation on the structure

  dynamics

  and conformational equilibrium of PKA-C using atomistic molecular dynamics simulations. We found that the myristoyl group inserts into the hydrophobic pocket and leads to a tighter packing of the A-helix against the core of the enzyme. As a result

  the conformational dynamics of the A-helix are reduced and its motions are more coupled with the active site. Our simulations suggest that cation−π interactions among W30

  R190

  and R93 are responsible for coupling these motions. Two major conformations of the myristoylated N-terminus are the most populated: a long loop (LL conformation)

  similar to Protein Data Bank (PDB) entry 1CMK

  and a helix−turn−helix structure (HTH conformation)

  similar to PDB entry 4DFX

  which shows stronger coupling between the conformational dynamics observed at the A-helix and active site. The HTH conformation is stabilized by S10 phosphorylation of the kinase via ionic interactions between the protonated amine of K7 and the phosphate group on S10

  further enhancing the dynamic coupling to the active site. These results support a role of N-myristoylation in the allosteric regulation of PKA-C.

  Jiali Gao

  Susan S Taylor

  Christopher Mcclendon

  Gianluigi Veglia

  Masterson

  Larry

  Masterson

  University of Minnesota

  Hamline University

  Vanderbilt University

  Minneapolis

  Graduate Research Associate

  University of Minnesota

  Hamline University

  Visiting Research Professor

  Vanderbilt University

  Assistant Professor

  Hamline University

  Postdoctoral Associate

  University of Minnesota

  Associate Professor of Chemistry

  Saint Paul

  MN

  Hamline University

  Pre-Medical Faculty Advisor

  Hamline University