# Time-resolved structural studies of enzyme catalysis and regulation

> **NIH NIH R35** · UNIVERSITY OF NEBRASKA LINCOLN · 2024 · $269,775

## Abstract

ABSTRACT
Enzyme catalysis is one of the most important phenomena in biochemistry and yet is incompletely understood.
New time-resolved serial crystallography methods now allow enzyme catalysis to be observed in real time, in
near-physiological conditions, and at atomic resolution, allowing new classes of experiments to be performed.
The central goal of this proposal is to both develop and use innovative structural biology methods to understand
the underlying physical principles of enzyme function. We will use time-resolved serial crystallography to
determine how catalysis changes enzyme structure and dynamics in cysteine-dependent enzymes. Our initial
focus is on various enzymes in the DJ-1 superfamily involved in parkinsonian neurodegeneration, isocyanide
antibiotic destruction, and carbonyl stress mitigation. A second contributor to enzyme catalysis is quantum
mechanical effects, some of which are becoming accessible to large computational simulations and experimental
characterization. We will determine how neglected quantum mechanical effects affect enzyme catalysis by
incorporating time-resolved crystallography, computation, and biochemistry to investigate pervasive evidence of
quantum mechanical charge transfer in catalysis. These scientific goals will be pursued concurrently with the
development of new methods to expand the scope and power of time-resolved structural biology experiments
by reducing barriers to performing these experiments. In total, this work will use new technologies to improve
the understanding of fundamental enzymatic phenomena and broaden the application of time-resolved structural
biology.

## Key facts

- **NIH application ID:** 10842723
- **Project number:** 1R35GM153337-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** Mark A. Wilson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $269,775
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842723

## Citation

> US National Institutes of Health, RePORTER application 10842723, Time-resolved structural studies of enzyme catalysis and regulation (1R35GM153337-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10842723. Licensed CC0.

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