# PURINE/PYRIMIDINE METABOLISM IN TRICHOMONAS & GIARDIA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1993 · $196,587

## Abstract

Trichomoniasis and giardiasis are two prevalent parasitic diseases in the
world.  The lack of effective chemoprophylactic and chemotherapeutic
controls of them today are of great concern.  We have recently indicated
that Trichomonas and Giardia are both incapable of de novo synthesis of
purine and pyrimidine nucleotides, which may constitute a major
vulnerability for them.  Several major, indispensable salvage enzymes have
since been identified in these parasites, among which T. foetus IMP
dehydrogenase, T. foetus hypoxanthanine-guanine-xanthine
phosphoribosyltransferase and G. lamblia guanine phosphoribosyltransferase
have been each purified to homogeneity and characterized.  All three
enzymes demonstrated unique kinetic properties and distinctive substrate
specificities which may quality them as the chemotherapeutic targets.
Further studies of the kinetic isotope effects and the isotope exchange on
T. foetus IMP dehydrogenase will be performed for more understanding on the
mechanism of the enzyme-catalyzed reaction and the unusual properties of
its dinucleotide binding site.  Genes encoding these three enzymes will be
identified by polymerase chain reactions, cloned, sequenced and expressed
in bacteria, yeast, mammalian cells or baculovirus for high yields of
native proteins.  The recombinant enzymes thus produced and purified will
be further analyzed for detailed mechanisms of enzyme catalysis.  Their
primary structures derived from the encoding DNA sequences will be analyzed
by computer modelings coupled with site-directed mutagenesis for
elucidation of tertiary protein structures.  In the long-term future plan,
pure proteins will be crystallized for X-ray diffraction analysis of the
three dimensional structures and comparisons among the protein structures
for structure-function relationships for specific inhibitor designs.  A
hypoxanthine/guanine transporter was recently identified in T. foetus.  It
is apparently essential for the survival of this parasite in its wild-type.
We will try to identify the transporter by inhibitor studies and isolate
this transporter by photoaffinity labeling and develop it as a new target
of anti-trichomonial chemotherapy for the future.

## Key facts

- **NIH application ID:** 3128775
- **Project number:** 5R01AI019391-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** Ching Chung WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $196,587
- **Award type:** 5
- **Project period:** 1982-08-01 → 1997-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128775

## Citation

> US National Institutes of Health, RePORTER application 3128775, PURINE/PYRIMIDINE METABOLISM IN TRICHOMONAS & GIARDIA (5R01AI019391-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128775. Licensed CC0.

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