Inhibitory substrate binding site of human indoleamine 2,3-dioxygenase

Changyuan Lu, Yu Lin, Syun-Ru Yeh

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

(Graph Presented) Human indoleamine 2,3-dioxygenase (hIDO) is an intracellular heme-containing enzyme, which catalyzes the initial and rate-determining step of L-tryptophan (L-Trp) metabolism via the kynurenine pathway. Due to its immunosuppressive function, hIDO has been recognized as an important drug target for cancer. Here we report evidence supporting the presence of an inhibitory substrate binding site (Si) in hIDO that is capable of binding molecules with a wide variety of structures, including substrates (L-Trp and 1-methyl-L-tryptophan), an effector (3-indole ethanol), and an uncompetitive inhibitor (Mitomycin C). The data offer useful guidelines for future development of more potent hIDO inhibitors; they also call for the re-evaluation of the action mechanism of Mitomycin C (MtoC), a widely used antitumor chemotherapeutic agent.

Original languageEnglish (US)
Pages (from-to)12866-12867
Number of pages2
JournalJournal of the American Chemical Society
Volume131
Issue number36
DOIs
StatePublished - Sep 16 2009

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Binding sites
Binding Sites
Tryptophan
Mitomycin
Substrates
Metabolism
Ethanol
Enzymes
Kynurenine
Molecules
Immunosuppressive Agents
Heme
Antineoplastic Agents
Guidelines
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Inhibitory substrate binding site of human indoleamine 2,3-dioxygenase. / Lu, Changyuan; Lin, Yu; Yeh, Syun-Ru.

In: Journal of the American Chemical Society, Vol. 131, No. 36, 16.09.2009, p. 12866-12867.

Research output: Contribution to journalArticle

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