# Structure and function of nucleotide sugar transporters.

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $323,400

## Abstract

Project summary
 Nucleotide sugar transporters (NSTs) are a family of proteins that are a critical part of the glycosylation
machinery in all eukaryotes as they are responsible for transporting nucleotide sugars from the cytoplasm,
where they are synthesized, into the Golgi lumen where they are then utilized by glycosyltransferases to
glycosylate proteins and lipids. NSTs provide an additional essential role of transporting the nucleotide
monophosphate byproduct of the glycosyltransferase reaction, which is inhibitory towards glycosyltransferases,
back to the cytoplasm where it can be recycled. Since NST activity controls the concentrations of both
nucleotide sugars and nucleotide monophosphates in the Golgi lumen, disruption of NST activity can have
many adverse physiological effects as is seen in a number of diseases caused by either mutations in NST
genes or dysregulation of NST activity. However, selective inhibition of NSTs also has the potential to be
exploited for therapeutic benefit in targeting parasites that depend on particular glycoconjugates for virulence
as well as in blocking certain glycosylation patterns that promote tumor metastasis. Our long-term goal is to
understand the molecular details that underlie substrate recognition, substrate selectivity, and the mechanism
of transport of NSTs. Although NSTs were first described nearly four decades ago, many of these questions
remain largely unanswered, primarily due to a lack of structural information for NSTs as well as limited
methods for biochemical characterization of this family of proteins. To overcome these obstacles, we have
developed methods to express, purify, and crystallize a mammalian NST, the mouse CMP-sialic acid
transporter (CST). We have also developed novel binding and transport assays that will allow us to address
questions regarding substrate recognition and selectivity. These methods will allow us to determine high-
resolution structures of CST in complex with its substrates CMP and CMP-sialic acid, as well as structures that
represent different states of the transport cycle. These structures combined with biochemical studies will
answer the fundamental questions regarding the structure-function relationship of NSTs, which will further our
understanding of the role NSTs play in physiology and aid in the development of drugs to target NSTs.

## Key facts

- **NIH application ID:** 10132193
- **Project number:** 5R01GM130909-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Isabelle Rhyssa Joe Eduria Baconguis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,400
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132193

## Citation

> US National Institutes of Health, RePORTER application 10132193, Structure and function of nucleotide sugar transporters. (5R01GM130909-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132193. Licensed CC0.

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