Ligand and Substrate Migration in Human Indoleamine 2,3-Dioxygenase |
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| Authors: | Elena Nickel Karin Nienhaus Changyuan Lu Syun-Ru Yeh G. Ulrich Nienhaus |
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| Affiliation: | From the ‡Institute of Biophysics, University of Ulm, 89069 Ulm, Germany, ;the §Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, ;the ¶Institute of Applied Physics and Center for Functional Nanostructures, Karlsruhe Institute of Technology, 76128 Karlsruhe, Germany, and ;the ‖Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 |
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| 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, CO escapes 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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