How is the distal pocket of a heme protein optimized for binding of tryptophan?
Article first published online: 22 NOV 2012
© 2012 The Authors Journal compilation © 2012 FEBS
Volume 279, Issue 24, pages 4501–4509, December 2012
How to Cite
Chauhan, N., Basran, J., Rafice, S. A., Efimov, I., Millett, E. S., Mowat, C. G., Moody, P. C. E., Handa, S. and Raven, E. L. (2012), How is the distal pocket of a heme protein optimized for binding of tryptophan?. FEBS Journal, 279: 4501–4509. doi: 10.1111/febs.12036
- Issue published online: 4 DEC 2012
- Article first published online: 22 NOV 2012
- Accepted manuscript online: 19 OCT 2012 12:00AM EST
- Manuscript Accepted: 16 OCT 2012
- Manuscript Revised: 15 OCT 2012
- Manuscript Received: 17 SEP 2012
- The Wellcome Trust. Grant Numbers: 083636, WT087777MA
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.