Density Functional Theory Study on a Missing Piece in Understanding of Heme Chemistry: The Reaction Mechanism for Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase.
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 23-dioxygenase (TDO) are heme-containing dioxygenases and catalyze oxidative cleavage of the pyrrole ring of L-tryptophan. On the basis of three recent crystal structures of these heme-containing dioxygenases, two new mechanistic pathways were propose...
| Publicado en: | Journal of the American Chemical Society Vol. 130; no. 37; pp. 12299 - 12310 |
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| Autores principales: | , , , , |
| Formato: | Artículo |
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American Chemical Society
9/17/2008
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=34543293&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 34543293 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 9/17/2008 vid: 130 iid: 37 pid: 997 pub: American Chemical Society artinfo: ui: 34543293 10.1021/ja803107w ppf: 12299 ppct: 11 formats: tig: atl: Density Functional Theory Study on a Missing Piece in Understanding of Heme Chemistry: The Reaction Mechanism for Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase. aug: au: Chung, Lung Wa Li, Xin Sugimoto, Hiroshi Shiro, Yoshitsugu Morokuma, Keiji affil: Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto 606-8103, Japan Biometal Science Laboratory, RIKEN SPring-8 Center, Hari,na Institute, Hyogo 679-5148, Japan su: Density functionals Heme oxygenase Heme Tryptophan oxygenase Tryptophan Electrophiles Imidazoles sug: subj: Density functionals Heme oxygenase Heme Tryptophan oxygenase Tryptophan Electrophiles Imidazoles ab: Indoleamine 2,3-dioxygenase (IDO) and tryptophan 23-dioxygenase (TDO) are heme-containing dioxygenases and catalyze oxidative cleavage of the pyrrole ring of L-tryptophan. On the basis of three recent crystal structures of these heme-containing dioxygenases, two new mechanistic pathways were proposed by several groups. Both pathways start with electrophilic addition of the Fe(ll)-bound dioxygen concerted with proton transfer (oxygen ene-type reaction), followed by either formation of a dioxetane intermediate or Criegee-type rearrangement. However, density functional theory (DFT) calculations do not support the proposed concerted oxygen ene-type and Criegee-type rearrangement pathways. On the basis of DFT calculations, we propose a new mechanism for dioxygen activation in these heme systems. The mechanism involves (a) direct electrophilic addition of the Fe(ll)-bound oxygen to the C2 or C3 position of the indole in a closed-shell singlet state or (b) direct radical addition of the Fe(lll)-superoxide to the 02 position of the indole in a triplet (or open-shell singlet) state. Then, a radical-recombination or nearly barrierless charge-recombination step from the resultant diradical or zwitterionic intermediates, respectively, proceeds to afford metastable dioxetane intermediates, followed by ring-opening of the dioxetanes. Alternatively, homolytic 0-0 bond cleavage from the diradical intermediate followed by oxo attack and facile C2-C3 bond cleavage could compete with the dioxetane formation pathway. Effects of ionization of the imidazole and negatively charged oxyporphyrin complex on the key dioxygen activation process are also studied. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2008 holdings: @attributes: islocal: N |
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