# Structure-Function Relationships in the Tautomerase Superfamily

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $289,960

## Abstract

The annotation of proteins with unknown functions discovered in genome projects is a key goal for the effective
use of genomic data in the treatment of disease in humans and in other organisms. It remains an extremely
difficult problem, but real progress has been made using the concept of functionally diverse superfamilies. The
work proposed here uses an integrated computational/experimental strategy to enhance current approaches
for the assignment of function in the mechanistically diverse tautomerase superfamily (TSF). Exploitation of
key features of the TSF (such as the ease of biochemical characterization) that make it a good model system
for the proposed aims lays the groundwork for application of these methods to all other superfamilies. This will
lead to a sustained improvement in our ability to use structure-function relationships on a large scale to inform
function prediction. The proposed work will address fundamental questions about structure-function
relationships in TSF enzymes and in other superfamilies using the TSF as a model system. It will move
sequence similarity network (SSN) technology forward in the areas of identifying and exploiting linkers, mining
metagenomic sequences, and genome context networks. These methodologies can be applied to all
superfamilies. It will characterize the macrophage migration inhibitory factor (MIF) subgroup of the TSF, the
subgroup with the most direct medical relevance. The phylogenetic distribution of MIF is the broadest of the 5
subgroups in the TSF. Mammalian MIFs are proinflammatory cytokines, but little is known about the functions
in bacteria, fungi, and other organisms. The work will be accomplished in three specific aims. These aims are
to: (1) investigate how active site sequences and structures diverge to generate new functions; (2) explore
sequence length and oligomer size in the evolution of structure and activity; and (3) examine genomic context
and biological function in the TSF. The results will also address our long-term goals, which are to obtain a
more comprehensive understanding of the relationship between structure and function in enzyme-catalyzed
reactions, and how these features change to create new activities. The results will advance our understanding
of the functions of bacterial and parasitic MIFs and their relationships to the mammalian ones, which are
implicated in multiple inflammatory disorders, and provide insight into the evolution of enzyme activities, which
has implications for the development of drug resistance in microorganisms.

## Key facts

- **NIH application ID:** 10202646
- **Project number:** 5R01GM129331-04
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** CHRISTIAN P. WHITMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $289,960
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202646

## Citation

> US National Institutes of Health, RePORTER application 10202646, Structure-Function Relationships in the Tautomerase Superfamily (5R01GM129331-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10202646. Licensed CC0.

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