# Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $690,150

## Abstract

Project Summary:
This project is focused on understanding the physical and mechanistic properties of enzymes that underlie
their exquisite function. In recent years, protein motions have been implicated as essential to achieve an
extremely rapid catalysis of bond cleavage events at enzyme active sites. Methodology for the spatial and
temporal resolution of such protein motions has been developed using enzyme prototypes that catalyze
hydrogen and methyl transfer reactions. These studies are now being extended to the TIM barrel family of
enzymes that represent 10% of known enzyme structures and catalyze 5 out of 7 known EC classes. With this
knowledge in hand, new approaches arise for protein redesign, de novo design and drug targeting. A second
emerging area in biological catalysis concerns the post-translational modification of peptides that have been
synthesized at the ribosome. A combination of structural and biochemical probes is addressing the enigmatic
pathway that produces the bacterial cofactor and vitamin, pyrroloquinoline quinone. As the result of a number
of recent breakthrough observations, each of the catalysts within the pathway is now amenable for detailed
mechanistic study. These enzymes have little or no precedence in humans, making the PQQ pathway a
possible new target for antibiotic development.

## Key facts

- **NIH application ID:** 10636781
- **Project number:** 5R35GM118117-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** JUDITH P KLINMAN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $690,150
- **Award type:** 5
- **Project period:** 2016-04-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10636781

## Citation

> US National Institutes of Health, RePORTER application 10636781, Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis (5R35GM118117-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10636781. Licensed CC0.

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