# Structural Basis of Metallocofactor Delivery and Repair

> **NIH NIH F31** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $46,752

## Abstract

PROJECT SUMMARY/ABSTRACT
Complex and reactive metallocofactors are often responsible for challenging chemistry that is critical to cellular
metabolism. It is therefore not surprising that the transport of these cofactors to their target enzymes often
involves multiple proteins and complex delivery pathways. Mutations in any of these components may result in
a breakdown of the pathway causing deficits in the overall activity of the target enzyme and leading to a disease
state, as in the case with the vitamin B12 (cobalamin, Cbl) delivery pathway. In this proposal, we will study
enzymes from humans, Methylobacterium extorquens and Cupriavidus metallidurans in order to determine the
molecular mechanisms of Cbl transport and installation. Our approach involves the use of a variety of biophysical
methods that will allow us to visualize the interactions between a G-protein chaperone and its target Cbl-
dependent mutase in the final step of the Cbl delivery pathway. This work will inform on the structural basis of
chaperone-mediated delivery and repair of Cbl. By combining X-ray crystallography, electron microscopy and
electron paramagnetic resonance spectroscopy, we will explore the molecular mechanism of action of the G-
protein chaperones involved in the installation and repair of adenosylcobalamin in their target mutases.

## Key facts

- **NIH application ID:** 10318598
- **Project number:** 5F31GM131648-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Francesca Vaccaro
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318598

## Citation

> US National Institutes of Health, RePORTER application 10318598, Structural Basis of Metallocofactor Delivery and Repair (5F31GM131648-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10318598. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*