| Title: | "A single amino acid residue regulates the substrate affinity and specificity of indoleamine 2,3-dioxygenase" |
| Author(s): | Yuasa HJ; Sugiura M; Harumoto T; |
| Address: | "Laboratory of Biochemistry, Department of Chemistry and Biotechnology, Faculty of Science and Technology, National University Corporation Kochi University, Kochi, 780-8520, Japan. Electronic address: julie@kochi-u.ac.jp. Department of Chemistry, Biology, and Environmental Sciences, Faculty of Science, National University Corporation Nara Women's University, Nara, 630-8506, Japan" |
| DOI: | 10.1016/j.abb.2017.12.019 |
| ISSN/ISBN: | 1096-0384 (Electronic) 0003-9861 (Linking) |
| Abstract: | "Indoleamine 2,3-dioxygenase (IDO) is a heme-containing enzyme that catalyses the oxidative cleavage of L-Trp. The ciliate Blepharisma stoltei has four IDO genes (IDO-I, -II, -III and -IV), which seem to have evolved via two sequential gene duplication events. Each IDO enzyme has a distinct enzymatic property, where IDO-III has a high affinity for L-Trp, whereas the affinity of the other three isoforms for L-Trp is low. IDO-I also exhibits a significant catalytic activity with another indole compound: 5-hydroxy-l-tryptophan (5-HTP). IDO-I is considered to be an enzyme that is involved in the biosynthesis of the 5-HTP-derived mating pheromone, gamone 2. By analysing a series of chimeric enzymes based on extant and predicted ancestral enzymes, we identified Asn131 in IDO-I and Glu132 in IDO-III as the key residues responsible for their high affinity for each specific substrate. These two residues were aligned in an identical position as the substrate-determining residue (SDR). Thus, the substrate affinity and specificity are regulated mostly by a single amino acid residue in the Blepharisma IDO-I and IDO-III enzymes" |
| Keywords: | "Amino Acid Sequence Amino Acids/*metabolism Catalysis Ciliophora/enzymology Gene Duplication Indoleamine-Pyrrole 2, 3, -Dioxygenase/chemistry/genetics/*metabolism Isoenzymes/chemistry/genetics/metabolism Kinetics Oxidation-Reduction Sequence Homology, Amino;" |
| Notes: | "MedlineYuasa, Hajime J Sugiura, Mayumi Harumoto, Terue eng Research Support, Non-U.S. Gov't 2017/12/31 Arch Biochem Biophys. 2018 Feb 15; 640:1-9. doi: 10.1016/j.abb.2017.12.019. Epub 2017 Dec 28" |
