# Generation and application of second messenger molecules by SMODS and SAVED

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $188,686

## Abstract

Project Summary/Abstract
 Nucleotide-based second messengers play important biological functions in living organisms. Among
various second messenger molecules, several of them are generated by families of NTases that belong to
Polb superfamily. In animals, cytosolic NTases OAS and cGAS generate 2’-5’-linked oligoadenylates and 2’-
5’-linked c-GAMP, respectively, both of which trigger innate immune response against viral and bacterial
infection. In bacteria, NTase DncV generates 3’-5’-linked cGAMP, which activates CapV to inhibit cell
growth. Using a combination of comparative genomics, sequence conservation, and structure analysis,
Aravind and coworkers uncovered a vast network of nucleotide-centric systems in bacteria. A family of
NTases named SMODS (secondary messenger oligo and dinucleotides synthase) was predicted to
generate second messengers. And several conserved domains were predicted to be receptors of the
second messengers generated by SMODS. Among the predicted receptors, the domain named SAVED
(SMODS-associated and fused to various effector domains) is the most abundant. With the exception of a
recent characterization of the product generated by one of SMODS, however, the predicted biochemical
and biological functions of SMODS and SAVED have not been experimentally tested. Employing
approaches of bioinformatics, biochemistry, and structural biology, we aim to pursue the following two lines
of investigation of SMODS and SAVED: 1) We will in vitro reconstitute the enzymatic activity of SMODS and
probe interaction between SAVED and the second messengers generated by SMODS; and 2) We will carry
out structural studies of SMODS and SAVED, SMODS in complex with its activator and substrates, and
SAVED in complex with the second messengers generated by SMODS.

## Key facts

- **NIH application ID:** 10078261
- **Project number:** 5R21AI150229-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Raven H Huang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,686
- **Award type:** 5
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10078261

## Citation

> US National Institutes of Health, RePORTER application 10078261, Generation and application of second messenger molecules by SMODS and SAVED (5R21AI150229-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10078261. Licensed CC0.

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