TY - CHAP
T1 - CHAPTER 9
T2 - Structure, Function and Regulation of Human Heme-based Dioxygenases
AU - Lewis-Ballester, Ariel
AU - Pham, Khoa N.
AU - Liao, Mingxiang
AU - Correia, Maria Almira
AU - Yeh, Syun Ru
N1 - Funding Information:
This work was supported by the National Science Foundation grant CHE-1404929 to S.-R.Y. and the National Institutes of Health Grants GM115773 and GM126297 to S.-R.Y., and GM44037 and DK26506 to M.A.C.
Funding Information:
This work was supported by the National science Foundation grant Che-1404929 to s.-r.y. and the National Institutes of health grants gM115773 and gM126297 to s.-r.y., and gM44037 and DK26506 to M.A.C.
Publisher Copyright:
© 2019 The Royal Society of Chemistry.
PY - 2019
Y1 - 2019
N2 - Dioxygenases belong to one of the three major classes of heme-based enzymes that utilize atmospheric O2 as a substrate. Oxidases, such as cytochrome c oxidase, reduce O2 to two water molecules by utilizing four electrons and four protons, and harness the redox energy to pump four protons across the protein matrix. Monooxygenases, such as P450, convert one atom of dioxygen to a water by consuming two electrons and two protons, and exploit the redox energy to insert the other oxygen atom into an organic substrate. Dioxygenases, including tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase 1 (IDO1), are unique, and least understood, as they are capable of inserting both atoms of O2 into Trp without using any electrons and protons. In Part A of this chapter, we review the structure and function relationships of human TDO and IDO1 and compare them with those of bacterial TDOs and two dioxygenase analogs, PrnB and MarE. In Part B we outline the mechanisms by which the TDO and IDO1 functions are regulated in vivo by a variety of effectors under various (patho)physiological conditions.
AB - Dioxygenases belong to one of the three major classes of heme-based enzymes that utilize atmospheric O2 as a substrate. Oxidases, such as cytochrome c oxidase, reduce O2 to two water molecules by utilizing four electrons and four protons, and harness the redox energy to pump four protons across the protein matrix. Monooxygenases, such as P450, convert one atom of dioxygen to a water by consuming two electrons and two protons, and exploit the redox energy to insert the other oxygen atom into an organic substrate. Dioxygenases, including tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase 1 (IDO1), are unique, and least understood, as they are capable of inserting both atoms of O2 into Trp without using any electrons and protons. In Part A of this chapter, we review the structure and function relationships of human TDO and IDO1 and compare them with those of bacterial TDOs and two dioxygenase analogs, PrnB and MarE. In Part B we outline the mechanisms by which the TDO and IDO1 functions are regulated in vivo by a variety of effectors under various (patho)physiological conditions.
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U2 - 10.1039/9781788012911-00181
DO - 10.1039/9781788012911-00181
M3 - Chapter
AN - SCOPUS:85056601299
T3 - RSC Metallobiology
SP - 181
EP - 221
BT - Dioxygen-dependent Heme Enzymes
A2 - Ikeda-Saito, Masao
A2 - Raven, Emma
PB - Royal Society of Chemistry
ER -