Ligand and substrate migration in human indoleamine 2,3-dioxygenase

Elena Nickel, Karin Nienhaus, Changyuan Lu, Syun-Ru Yeh, G. Ulrich Nienhaus

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Human indoleamine 2,3-dioxygenase (hIDO), a monomeric heme enzyme, catalyzes the oxidative degradation of L-Trp and other indoleamine derivatives. Using Fourier transform infrared and optical absorption spectroscopy, we have investigated the interplay between ferrous hIDO, the ligand analog CO, and the physiological substrate L-Trp. These data provide the long sought evidence for two distinct L-Trp binding sites. Upon photodissociation from the heme iron at T> 200 K,COescapes into the solvent. Concomitantly, L-Trp exits the active site and, depending on the L-Trp concentration, migrates to a secondary binding site or into the solvent. Although L-Trp is spectroscopically silent at this site, it is still noticeable due to its pronounced effect on the CO association kinetics, which are significantly slower than those of L-Trp-free hIDO. L-Trp returns to its initial site only after CO has rebound to the heme iron.

Original languageEnglish (US)
Pages (from-to)31548-31554
Number of pages7
JournalJournal of Biological Chemistry
Volume284
Issue number46
DOIs
StatePublished - 2009

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Carbon Monoxide
Heme
Ligands
Substrates
Iron
Binding Sites
Photodissociation
Infrared absorption
Fourier Analysis
Absorption spectroscopy
Light absorption
Catalytic Domain
Spectrum Analysis
Fourier transforms
Association reactions
Derivatives
Degradation
Kinetics
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Ligand and substrate migration in human indoleamine 2,3-dioxygenase. / Nickel, Elena; Nienhaus, Karin; Lu, Changyuan; Yeh, Syun-Ru; Nienhaus, G. Ulrich.

In: Journal of Biological Chemistry, Vol. 284, No. 46, 2009, p. 31548-31554.

Research output: Contribution to journalArticle

Nickel, Elena ; Nienhaus, Karin ; Lu, Changyuan ; Yeh, Syun-Ru ; Nienhaus, G. Ulrich. / Ligand and substrate migration in human indoleamine 2,3-dioxygenase. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 46. pp. 31548-31554.
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