Related Experiment Videos
Interactions between nitric oxide and indoleamine 2,3-dioxygenase.
Ben J Samelson-Jones1, Syun-Ru Yeh
1Department of Physiology and Biophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA.
Biochemistry
|July 13, 2006
Summary
Nitric oxide (NO) inhibits indoleamine 2,3-dioxygenase (IDO) by altering its heme structure and promoting degradation. L-tryptophan (L-Trp) binding prevents this NO-induced inactivation, revealing a key regulatory mechanism.
Area of Science:
- Biochemistry
- Enzymology
- Molecular Biology
Background:
- Indoleamine 2,3-dioxygenase (IDO) is crucial for L-tryptophan metabolism via the kynurenine pathway.
- IDO is induced during inflammation and its activity is modulated by nitric oxide (NO).
Purpose of the Study:
- To elucidate the molecular mechanisms of NO interaction with human recombinant IDO (hIDO).
- To understand how NO binding affects hIDO structure, activity, and degradation.
Main Methods:
- Optical absorption spectroscopy
- Resonance Raman spectroscopy
Main Results:
- NO binding induces conformational changes in hIDO's heme environment, leading to an out-of-plane deformed geometry.
- Under acidic conditions, NO binding can rupture the heme iron-His bond, forming a five-coordinate species.
- This NO-induced structural change leads to hIDO inactivation and proteasomal degradation.
- L-tryptophan (L-Trp) binding inhibits NO-induced bond breakage and protects hIDO.
Conclusions:
- NO regulates hIDO activity and degradation through direct molecular interactions.
- The regulatory mechanism is sensitive to cellular factors like NO concentration, pH, redox state, and L-Trp availability.