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

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

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20 Scopus citations


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
Issue number46
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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