How is the distal pocket of a heme protein optimized for binding of tryptophan?

Nishma Chauhan, Jaswir Basran, Sara A. Rafice, Igor Efimov, Elizabeth S. Millett, Christopher G. Mowat, Peter C E Moody, Sandeep Handa, Emma L. Raven*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

19 Citations (Scopus)


Indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase catalyze the O2-dependent oxidation of l-tryptophan to N-formylkynurenine. Both are heme-containing enzymes, with a proximal histidine ligand, as found in the globins and peroxidases. From the structural information available so far, the distal heme pockets of these enzymes can contain a histidine residue (in tryptophan 2,3-dioxygenases), an arginine residue and numerous hydrophobic residues that line the pocket. We have examined the functional role of each of these residues in both human indoleamine 2,3-dioxygenase and human tryptophan 2,3-dioxygenase. We found that the distal histidine does not play an essential catalytic role, although substrate binding can be affected by removing the distal arginine and reducing the hydrophobic nature of the binding pocket. We collate the information obtained in the present study with that reported in the available literature to draw comparisons across the family and to provide a more coherent picture of how the heme pocket is optimized for tryptophan binding.

Original languageEnglish
Pages (from-to)4501-4509
Number of pages9
JournalFEBS Journal
Issue number24
Publication statusPublished - 1 Dec 2012


  • dioxygenase
  • heme
  • iron
  • N-formylkynurenine
  • tryptophan

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