TY - JOUR
T1 - Ligand and substrate migration in human indoleamine 2,3-dioxygenase
AU - Nickel, Elena
AU - Nienhaus, Karin
AU - Lu, Changyuan
AU - Yeh, Syun Ru
AU - Nienhaus, G. Ulrich
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M109.039859
DO - 10.1074/jbc.M109.039859
M3 - Article
C2 - 19767648
AN - SCOPUS:70450267378
SN - 0021-9258
VL - 284
SP - 31548
EP - 31554
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -