Area of research
Physiology · Periodontics
Research interest
Research topics from publications: Imaging active site chemistry and protonation states: NMR crystallography of the tryptophan synthase α-aminoacrylate intermediate; Direct dynamic nuclear polarization of 15N and 13C spins at 14.1 T using a trityl radical and magic angle spinning. Representative work: Significance The determination of active site protonation states is critical for a full mechanistic understanding of enzymatic transformations. However, hydrogen atom positions are challenging to extract using the standard tools of structural biology. Here, we make use of a joint solid-state NMR, X-ray crystallography, and first-principles computational approach that enables the investigation of enzyme catalysis at this fine level of chemical detail. For tryptophan synthase, this allows us to peer along the reaction coordinates into and out of the α-aminoacrylate intermediate. Through this process, we are developing a high-resolution probe for structural biology that is keenly sensitive to h Abstract NMR-assisted crystallography – the synergistic combination of solid-state NMR, X-ray crystallography, and first-principles computational chemistry – holds remarkable promise for mechanistic enzymology: by providing atomic-resolution characterization of stable intermediates in the enzyme active site – including hydrogen atom locations and tautomeric equilibria – it offers insight into structure, dynamics, and function. Here, we make use of this combined approach to characterize the α-aminoacrylate intermediate in tryptophan synthase, a defining species for pyridoxal-5′-phosphate-dependent enzymes on the β-elimination and replacement pathway. By uniquely identifying the protonation st